Original Article
Leptin-Replacement Therapy for Lipodystrophy
N Engl J Med 2002; 346:570-578February 21, 2002
- Abstract
Background
The adipocyte hormone leptin is important in regulating energy homeostasis. Since severe lipodystrophy is associated with leptin deficiency, insulin resistance, hypertriglyceridemia, and hepatic steatosis, we assessed whether leptin replacement would ameliorate this condition.
Methods
Nine female patients (age range, 15 to 42 years; eight with diabetes mellitus) who had lipodystrophy and serum leptin levels of less than 4 ng per milliliter (0.32 nmol per milliliter) received recombinant methionyl human leptin (recombinant leptin). Recombinant leptin was administered subcutaneously twice a day for four months at escalating doses to achieve low, intermediate, and high physiologic replacement levels of leptin.
Results
During treatment with recombinant leptin, the serum leptin level increased from a mean (±SE) of 1.3±0.3 ng per milliliter to 11.1±2.5 ng per milliliter (0.1±0.02 to 0.9±0.2 nmol per milliliter). The absolute decrease in the glycosylated hemoglobin value was 1.9 percent (95 percent confidence interval, 1.1 to 2.7 percent; P=0.001) in the eight patients with diabetes. Four months of therapy decreased average triglyceride levels by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001) and liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent; P=0.002) in all nine patients and led to the discontinuation of or a large reduction in antidiabetes therapy. Self-reported daily caloric intake and the measured resting metabolic rate also decreased significantly with therapy. Overall, recombinant leptin therapy was well tolerated.
Conclusions
Leptin-replacement therapy improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. Leptin deficiency contributes to the insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.
Media in This Article
Figure 3
Effects of Leptin-Replacement Therapy on Insulin Sensitivity and Triglyceride Levels in Patient 1 while She Was Following a Diet Containing 1900 kcal per Day.Figure 2
Mean (±SE) Plasma Glucose Levels in Response to an Insulin-Tolerance Test (Panel A) and an Oral Glucose-Tolerance Test (Panel B) in Nine Patients at Base Line and after Four Months of Leptin-Replacement Therapy.Article Activity
- Article
The adipocyte hormone leptin has a central role in energy homeostasis.1 Serum leptin levels are directly proportional to adipocyte mass.2 Normally, a low leptin level signals starvation and directs the body to adapt to this condition.3 One way to gain insight into the physiological importance of leptin in humans is to study the conditions associated with its absence or deficiency.
Patients with a complete deficiency of leptin as a result of mutations in the leptin gene are morbidly obese from infancy and have a number of hormonal abnormalities, including insulin resistance and hypogonadotropic hypogonadism.4 Physiologic replacement with recombinant leptin for one year in one such patient led to a substantial weight reduction and an improvement in the hormonal abnormalities.5
Severe lipodystrophy, caused by a deficiency or destruction of adipose cells, is another state characterized by low leptin levels.6 Other abnormalities in this condition include hypertriglyceridemia and severe insulin resistance, which is usually accompanied by diabetes mellitus.6,7 There are several genetic and acquired forms of lipodystrophy in humans, and studies of a variety of genetically engineered animal models6,8 demonstrated that the metabolic abnormalities develop as a consequence of fat loss.9 Why is adipose tissue so vital to the prevention of the metabolic abnormalities? One hypothesis is that the adipocyte hormone leptin has a critical role in preventing the insulin resistance and hypertriglyceridemia of lipodystrophy. Interestingly, leptin-replacement therapy at a level meant to achieve physiologic levels led to a dramatic improvement in insulin resistance, hyperglycemia, hypertriglyceridemia, and hepatic steatosis in a mouse model of lipodystrophy.10 Therefore, we sought to determine whether such treatment would improve the insulin resistance, diabetes, and hypertriglyceridemia of patients with lipodystrophy.
Methods
Patients
Eligible patients had to have low serum leptin levels (less than 3 ng per milliliter [0.24 nmol per milliliter] in the case of male patients and less than 4 ng per milliliter [0.32 nmol per milliliter] in the case of female patients) in association with lipodystrophy and at least one of the following metabolic abnormalities: diabetes mellitus, defined according to the criteria of the American Diabetes Association11; serum triglyceride levels (measured after an overnight fast) of more than 200 mg per deciliter (2.23 mmol per liter); and fasting serum insulin levels of more than 30 μU per milliliter (215 pmol per liter). Table 1Table 1
Base-Line Characteristics of the Patients and Treatment Regimens at Base Line and after Four Months of Recombinant Leptin. summarizes the base-line clinical characteristics of the nine patients treated in the study. The patients ranged from 15 to 42 years of age. All nine were female, although the study was open to both sexes. Five of the nine patients had congenital generalized lipodystrophy, or the Seip–Berardinelli syndrome, characterized by generalized fat loss from birth in association with other clinical criteria (Online Mendelian Inheritance in Man [OMIM]13 number 269700).14 One patient had Dunnigan's familial partial lipodystrophy (OMIM13 number 151660).15,16 The other three patients had acquired generalized lipodystrophy.Study Design
The study was designed as a prospective, open-label study at the Diabetes Branch of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) and the University of Texas Southwestern Medical Center in Dallas. Amgen (Thousand Oaks, Calif.) provided recombinant methionyl human leptin (recombinant leptin). Although Amgen provided the recombinant leptin, the data were held by the academic investigators. The response of each patient was compared with her base-line values. Because of the rarity and clinical variability of lipodystrophy syndromes, it was not feasible to include a randomized, placebo-treated control group. The study was approved by the institutional review boards of the study centers, and written informed consent was obtained from all patients. The study was initiated in August 2000, and data collection was completed at the end of June 2001.
The patients were evaluated as inpatients before treatment and again after one, two, and four months of recombinant leptin therapy. All patients had been receiving stable doses of other medications for at least six weeks (range, six weeks to eight months) before they began to receive leptin-replacement therapy. During the study, the doses of hypoglycemic drugs were tapered or the treatments discontinued as needed (Table 1).
Recombinant leptin was administered subcutaneously every 12 hours. The physiologic replacement dose was estimated to be 0.03 mg per kilogram of body weight per day for girls under 18 years of age and 0.04 mg per kilogram per day for women on the basis of information provided by the manufacturer. These doses are approximately 1/10 of the dose most commonly used in obesity trials. Patients were treated with 50 percent of the replacement dose for the first month, 100 percent for the second month, and 200 percent for the third and fourth months.
Biochemical Analyses
Serum glucose and triglyceride levels were determined according to standard methods with the use of automated equipment (Hitachi, Boehringer Mannheim, Indianapolis) at the NIH and a Beckman instrument (Fullerton, Calif.) at the University of Texas Southwestern Medical Center. Glycosylated hemoglobin values were measured by ion-exchange high-performance liquid chromatography (Bio-Rad Laboratories, Hercules, Calif.), and levels of free fatty acids were measured with use of a commercial kit (Wako, Richmond, Va.). Serum insulin levels were determined by immunoassays with the use of reagents provided by Abbott Instruments (Abbott Park, Ill.) at the NIH and a commercial kit (Linco Research, St. Charles, Mo.) at the University of Texas Southwestern Medical Center. Serum leptin levels were determined by immunoassays with the use of a commercial kit (Linco Research).
Procedures
The resting metabolic rate was measured (Deltatrac equipment, Sensormedics, Yorba Linda, Calif.) between 6 a.m. and 8 a.m. while patients rested, after an overnight fast of more than eight hours. After an overnight fast, each patient underwent an oral glucose-tolerance test in which 75 g of dextrose was administered orally.
A high-dose insulin-tolerance test was performed with the use of 0.2 U of regular insulin per kilogram to assess the patients' sensitivity to insulin. The K constant (the rate of glucose disappearance as a reflection of the body's overall sensitivity to insulin) was calculated as the rate constant for the decrease in blood glucose levels after the intravenous administration of insulin with the use of first-order kinetics.17 The seven patients who were seen at the NIH Clinical Center reported their daily food intake at base line and at four months using a standardized questionnaire.18
Body fat was determined with use of a dual-energy x-ray absorptiometer (model QDR 4500, Hologic, Bedford, Mass.).19 Axial T1-weighted magnetic resonance imaging of the liver was performed with use of a 1.5-T scanner (General Electric Medical Systems, Milwaukee, at the NIH and Philips Medical Systems, Best, the Netherlands, at the University of Texas Southwestern Medical Center).20 Liver volumes were calculated with use of the MEDx image-analysis software package (Sensor Systems, Sterling, Va.).
Statistical Analysis
Values are presented as means ±SE. We used an analysis of variance with repeated measures to compare the study variables during various study periods. Skewed data on triglyceride levels and calculated K constants were log-transformed. We used a paired t-test wherever it was applicable to compare base-line data with data obtained at various times. We analyzed changes in plasma glucose levels during the oral glucose-tolerance test using a two-factor analysis of variance in which the study period and the time during the test were modeled as repeated factors. We calculated 95 percent confidence intervals for the differences between the means according to the method of Hahn and Meeker.21 The manuscript was jointly written by a committee of the investigators.
Results
Base-Line Characteristics of the Patients
Eight of the nine patients in the study had diabetes (Table 1), and all nine had hyperlipidemia (Table 2Table 2
Metabolic Values before and during Treatment with Recombinant Leptin.). All patients with diabetes were receiving medications for their diabetes before the study began, and four of the nine patients received lipid-lowering therapy (Table 1). Their average glycosylated hemoglobin value was 9.1±0.5 percent (normal, less than 5.6 percent) at the base-line evaluation. The mean triglyceride levels were elevated at base line, at 1405 mg per deciliter (16 mmol per liter) (range, 322 to 7420 mg per deciliter [3.6 to 83.8 mmol per liter]; normal range, 35 to 155 mg per deciliter [0.4 to 1.7 mmol per liter]). Free fatty acid levels were also increased, at a mean of 1540±407 μmol per liter (normal, 350 to 550).Changes in Circulating Leptin Levels
The mean serum leptin level was 1.3±0.3 ng per milliliter (0.1±0.02 nmol per milliliter) at base line (Table 1) and increased to 2.3±0.5 ng per milliliter (0.2±0.04 nmol per milliliter) at the end of the first month of therapy, to 5.5±1.2 ng per milliliter (0.4±0.1 nmol per milliliter) at the end of the second month, and to 11.1±2.5 ng per milliliter (0.9±0.2 nmol per milliliter) at the end of the fourth month. Thus, the administration of recombinant leptin resulted in approximately normal serum leptin levels in these patients.12
Changes in Metabolic Control
The first patient treated in this study (Patient 1) was also the most severely affected,22 and her clinical course is shown in Figure 1Figure 1
Clinical Course of Patient 1, as Assessed by Changes in Mean Triglyceride Levels, Glycosylated Hemoglobin Values, and Serum Leptin Values.. Leptin-replacement therapy had a marked effect in this patient and in the group as a whole.22 Before the initiation of leptin therapy, the eight patients with diabetes had poor metabolic control, with a mean glycosylated hemoglobin value of 9.1±0.5 percent. After four months of leptin-replacement therapy, the glycosylated hemoglobin value decreased by a mean of 1.9 percentage points (95 percent confidence interval, 1.1 to 2.7; P=0.001). The individual responses of the patients are provided in Table 2. Glycemic control improved despite the fact that antidiabetic therapy was decreased or discontinued during the four months of leptin-replacement therapy (Table 1).At the end of four months of recombinant leptin therapy, the fasting triglyceride levels had fallen by 60 percent (95 percent confidence interval, 43 to 77 percent; P<0.001). The individual responses of the patients are given in Table 2. During the same period, fasting levels of free fatty acids fell from a mean of 1540±407 μmol per liter to 790±164 μmol per liter (P=0.05).
The insulin-tolerance test showed that plasma glucose levels had significantly decreased at the end of four months of therapy (Figure 2AFigure 2
Mean (±SE) Plasma Glucose Levels in Response to an Insulin-Tolerance Test (Panel A) and an Oral Glucose-Tolerance Test (Panel B) in Nine Patients at Base Line and after Four Months of Leptin-Replacement Therapy.). The K constant (the rate of glucose disappearance) increased from 0.007±0.001 to 0.017±0.004, indicating an improvement in whole-body sensitivity to insulin (P=0.04). Furthermore, the glucose levels measured in response to an oral glucose load (75 g of dextrose) were significantly lower than the base-line levels (Figure 2B).Since all patients derived clinically significant benefit from leptin-replacement therapy, all continue to receive treatment.
Changes in Liver Volume and Liver-Function Tests
At base line, the mean liver volume was 3097±391 ml (approximately four times the volume in age- and sex-matched persons of normal weight). Leptin decreased the liver volume by an average of 28 percent (95 percent confidence interval, 20 to 36 percent) from base line (P=0.002). The decrease in liver size was associated with an improvement in liver-function tests. Base-line alanine aminotransferase levels had decreased from 66±16 to 24±4 U per liter at the end of four months of therapy (P=0.02). Likewise, serum aspartate aminotransferase levels were 53±12 U per liter at base line and 21±2 U per liter at the end of four months of therapy (P=0.03).
Changes in Energy Balance
Data on self-reported daily caloric intake were available for seven patients. The daily caloric intake decreased from a mean of 2680±250 kcal per day at base line to 1600±150 kcal per day after four months of leptin-replacement therapy (P=0.005). There was a parallel decrease in the resting metabolic rate (measured in all nine patients), from 1920±150 to 1580±80 kcal per day (P=0.003).
All but one patient (Patient 3) had lost weight at the end of four months of treatment (mean weight loss, 3.6±0.9 kg; range, –1.7 to 7.3). An important fraction of the weight loss (50 to 65 percent) was attributed to the decrease in liver volume.
Adverse Events
Patient 1 had a severe episode of nausea and vomiting after the first dose of recombinant leptin. After the second dose, Patient 6 had an exacerbation of hypertension associated with flushing. Patient 7 was hospitalized for a streptococcal infection during the third month of therapy. All these events resolved, and none recurred with the continuation of therapy. No skin reactions at injection sites were reported or observed.
Withdrawal of Recombinant Leptin
Since the patients had reduced their intake of food during leptin-replacement therapy, we assessed whether the metabolic values were maintained in the presence of a reduced intake of food. Patient 1 was admitted to the NIH Clinical Center and received 1900 kcal per day (55 percent carbohydrates, 25 percent fat, and 20 percent protein), which was based on the patient's reported intake of food during leptin-replacement therapy and on a measurement of the resting metabolic rate, in the form of three meals and two snacks. Leptin-replacement therapy was stopped after day 5. Plasma glucose levels were measured before each meal and at bedtime, and the daily averages were calculated. Fasting plasma triglyceride and insulin levels were determined. Within 48 hours after the withdrawal of recombinant leptin, the fasting plasma triglyceride and insulin levels began to increase. The effects were corrected by the resumption of leptin-replacement therapy (Figure 3Figure 3
Effects of Leptin-Replacement Therapy on Insulin Sensitivity and Triglyceride Levels in Patient 1 while She Was Following a Diet Containing 1900 kcal per Day.).Discussion
Leptin-replacement therapy led to clear and dramatic metabolic benefits in this group of nine patients with lipodystrophy and leptin deficiency. Treatment with recombinant leptin resulted in an absolute reduction in the glycosylated hemoglobin value of 1.9 percent. Such a reduction is predicted to decrease the relative risk of retinopathy by approximately 48 percent and nephropathy by approximately 22 percent in the diabetic population.23 Furthermore, triglyceride levels fell by 60 percent, and such a reduction is predicted to decrease the relative risk of cardiovascular events in the general population by 35 to 65 percent.24,25
To date, the insulin resistance and hypertriglyceridemia that characterize lipodystrophy have been refractory to treatment.26 Thiazolidinediones appear to be the most effective therapy, albeit an imperfect one.27 Commonly, this condition is managed with a combination of medications, including high doses of insulin, oral hypoglycemic agents (e.g., metformin and thiazolidinediones), and lipid-lowering drugs (e.g., fibrates and statins). Despite such therapy, patients continue to have severe hypertriglyceridemia, leading to recurrent attacks of acute pancreatitis; severe hyperglycemia, posing risks of diabetic retinopathy and nephropathy; and nonalcoholic steatohepatitis, which can result in cirrhosis. Leptin-replacement therapy appears to have the potential to prevent all these complications.
Our results also demonstrate a novel action of leptin. Leptin appears to provide a signal that regulates total-body sensitivity to insulin and triglyceride levels in addition to its known role in the control of energy homeostasis.
Although our study was not randomized, the improved metabolic control appeared to be due to leptin-replacement therapy rather than to an improvement in general compliance associated with participation in a study.
An important unanswered question is the effect of decreased food intake on the changes in metabolic values in this study. In patients with lipodystrophy, limiting caloric intake improves glucose and lipid abnormalities.28 Leptin-replacement therapy reduced food intake in our patients. However, in an analysis involving Patient 1, we observed an additional effect of leptin-replacement therapy on insulin sensitivity and triglyceride metabolism that was independent of food intake. In this patient, fasting insulin and triglyceride levels increased within two and four days, respectively, after recombinant leptin was withdrawn even though the level of food intake remained constant. Similar data have been reported in paired-feeding experiments (with or without leptin administration) involving lipoatrophic mice.10,29
Leptin has been identified as the missing hormone in obese (ob/ob) mice.1 In these mice, leptin-replacement therapy decreased food intake and body weight.30-32 Because of such initial observations, obesity has been the focus of most therapeutic trials with leptin. However, most obese people have high serum leptin levels and are therefore presumed to have leptin resistance.33 Thus far, the average weight loss in obese persons has not been significant,34 except in patients with congenital leptin deficiency.5
Study of various mouse models of lipodystrophy suggests that the absence of adipose tissue is the cause of insulin resistance in this syndrome.35-37 The demonstration that transplantation of adipose tissue into mice with lipodystrophy ameliorates insulin resistance and improves metabolic control provides strong support for this hypothesis.9 However, why adipose tissue was required to maintain whole-body sensitivity to insulin has remained unclear. Shimomura et al. tested the efficacy of leptin replacement in a mouse model and observed a dramatic improvement in glucose and triglyceride levels and hepatic steatosis.10 Taken together, these observations and our results suggest that leptin controls the majority of the regulatory action of adipose tissue on whole-body sensitivity to insulin.
In our study, leptin-replacement therapy was associated with a decline in the resting metabolic rate. This finding is parallel to observations in patients with a congenital absence of leptin.33 Although the mechanism of this effect is unclear, we presume that the leptin-induced decrease in food intake reduces diet-induced thermogenesis.
Unger and colleagues have reported that leptin administration in Zucker rats corrects steatosis in a variety of organs that act as sites of lipid accumulation, such as the liver, islet cells, and the heart.38,39 The accumulation of lipids at these sites may represent a spillover phenomenon resulting from the fact that adipocytes have reached their capacity to store triglycerides. In patients with lipodystrophy, these organs are the only sites that can store lipids. Leptin treatment of mice with lipodystrophy causes a dramatic decrease in hepatic stores of triglycerides. In parallel, leptin-replacement therapy in our patients with lipodystrophy caused a significant reduction in liver volume.
The concept that adipose tissue is an endocrine organ was strongly supported by the discovery of leptin. Leptin has effects (direct or indirect) on the key organs of metabolism, including the brain, liver, muscle, fat, and pancreas. Leptin is certainly not the only circulating adipocyte signal.40-42 Lack of adipocytes should result in a deficiency of all fat-derived signals. On the basis of our findings, leptin deficiency appears to be the chief contributor to the metabolic abnormalities associated with lipodystrophy. Thus, severe lipodystrophy may be an important reason to consider leptin-replacement therapy. The optimal dose of recombinant leptin in patients with lipodystrophy, the role of leptin-replacement therapy in treating other insulin-resistance states, and the degree of leptin deficiency that will respond to leptin-replacement therapy remain to be determined.
Supported in part by grants from the NIH (RO1-DK54387 and MO1-RR00633) and from Amgen.
Drs. Wagner and DePaoli are employees of Amgen. Dr. Taylor is now an employee of Eli Lilly.
We are indebted to the following for their contribution to the study: Oksana Gavrilova, Monica Skarulis, Karim Calis, Beverley Adams-Huet, Jerry Payne, Bryan Fox, Nancy Sebring, Patti Riggs, Bernice Marcus-Samuels, Craig Cochran, Angela Osborn, Esther Bergman, nurses and clinical fellows, and the Metabolic Cart Consult Service.
Source Information
From the Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.A.O., E.R., A.A., M.L.R., S.I.T., P.G.), and the Clinical Center (A.P.), National Institutes of Health, Bethesda, Md.; the University of Texas Southwestern Medical Center at Dallas, Dallas (V.S., P.S., A.G.); and Amgen, Thousand Oaks, Calif. (A.J.W., A.M.D.).
Address reprint requests to Dr. Oral at the National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch, Bldg. 10, Rm. 8D20, Bethesda, MD 20892-1770, or at elif_arioglu@nih.gov.
- References
References
1
Zhang Y ,Proenca R ,Maffei M ,Barone M ,Leopold L ,Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432[Erratum, Nature 1995;374:479.]
CrossRef | Web of Science | Medline2
Considine RV ,Sinha MK ,Heiman ML , et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295
Full Text | Web of Science | Medline3
Ahima RS ,Prabakaran D ,Mantzoros C , et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996;382:250-252
CrossRef | Web of Science | Medline4
Montague CT ,Farooqi IS ,Whitehead JP , et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903-908
CrossRef | Web of Science | Medline5
Farooqi IS ,Jebb SA ,Langmack G , et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-884
Full Text | Web of Science | Medline6
Reitman ML ,Arioglu E ,Gavrilova O ,Taylor SI . Lipoatrophy revisited. Trends Endocrinol Metab 2000;11:410-416
CrossRef | Web of Science | Medline7
Lawrence RD . Lipodystrophy and hepatomegaly with diabetes, lipaemia, and other metabolic disturbances: a case throwing new light on the action of insulin. Lancet 1946;1:724-31, 773
CrossRef | Medline8
Magre J ,Delepine M ,Khallouf E , et al. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet 2001;28:365-370
CrossRef | Web of Science | Medline9
Gavrilova A ,Marcus-Samuels B ,Graham D , et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000;105:271-278
CrossRef | Web of Science | Medline10
Shimomura I ,Hammer RE ,Ikemoto S ,Brown MS ,Goldstein JL . Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999;401:73-76
CrossRef | Web of Science | Medline11
Peters AL ,Schriger DL . The new diagnostic criteria for diabetes: the impact on management of diabetes and macrovascular risk factors. Am J Med 1998;105:Suppl 1A:15S-19S
CrossRef | Medline12
Ruhl CE ,Everhart JE . Leptin concentrations in the United States: relations with demographic and anthropometric measures. Am J Clin Nutr 2001;74:295-301
Web of Science | Medline13
McKusick V. Online mendelian inheritance in man. Baltimore: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, 2001. (Accessed January 25, 2002, at http://www.ncbi.nlm.nih.gov/Omim.)
14
Garg A ,Fleckenstein JL ,Peshock RM ,Grundy SM . Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy. J Clin Endocrinol Metab 1992;75:358-361
CrossRef | Web of Science | Medline15
Garg A ,Peshock RM ,Fleckenstein JL . Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab 1999;84:170-174
CrossRef | Web of Science | Medline16
Cao H ,Hegele RA . Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 2000;9:109-112
CrossRef | Web of Science | Medline17
Harrison LC ,Martin FI ,Melick RA . Correlation between insulin receptor binding in isolated fat cells and insulin sensitivity in obese human subjects. J Clin Invest 1976;58:1435-1441
CrossRef | Web of Science | Medline18
Feskanich D ,Rimm EB ,Giovannucci EL , et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc 1993;93:790-796
CrossRef | Web of Science | Medline19
Lambrinoudaki I ,Georgiou E ,Douskas G ,Tsekes G ,Kyriakidis M ,Proukakis C . Body composition assessment by dual-energy x-ray absorptiometry: comparison of prone and supine measurements. Metabolism 1998;47:1379-1382
CrossRef | Web of Science | Medline20
Abate N ,Burns D ,Peshock RM ,Garg A ,Grundy SM . Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers. J Lipid Res 1994;35:1490-1496
Web of Science | Medline21
Hahn GJ, Meeker WQ. Statistical intervals: a guide for practitioners. New York: John Wiley, 1991.
22
Bolan C ,Arioglu Oral E ,Gorden E ,Taylor S ,Lietman SF . Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy. J Clin Endocrinol Metab 2002;87:380-384
CrossRef | Web of Science | Medline23
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-853[Erratum, Lancet 1999;354:602.]
CrossRef | Web of Science | Medline24
Kreisberg RA . Diabetic dyslipidemia. Am J Cardiol 1998;82:Suppl:67U-73U
CrossRef | Web of Science | Medline25
Gotto AM Jr . Triglyceride as a risk factor for coronary artery disease. Am J Cardiol 1998;82:22Q-25Q
Web of Science | Medline26
Garg A . Lipodystrophies. Am J Med 2000;108:143-152
CrossRef | Web of Science | Medline27
Arioglu E ,Duncan-Morin J ,Sebring N , et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med 2000;133:263-274
Web of Science | Medline28
Trygstad O ,Seip M ,Oseid S . Lipodystrophic diabetes treated with fenfluramine. Int J Obes 1977;1:287-292
Web of Science | Medline29
Ebihara K ,Ogawa Y ,Masuzaki H , et al. Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes 2001;50:1440-1448
CrossRef | Web of Science | Medline30
Campfield LA ,Smith FJ ,Guisez Y ,Devos R ,Burn P . Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-549
CrossRef | Web of Science | Medline31
Halaas JL ,Gajiwala KS ,Maffei M , et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-546
CrossRef | Web of Science | Medline32
Pelleymounter MA ,Cullen MJ ,Baker MB , et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-543
CrossRef | Web of Science | Medline33
Mantzoros CS ,Flier JS . Leptin as a therapeutic agent -- trials and tribulations. J Clin Endocrinol Metab 2000;85:4000-4002
CrossRef | Web of Science | Medline34
Heymsfield SB ,Greenberg AS ,Fujioka K , et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999;282:1568-1575
CrossRef | Web of Science | Medline35
Burant CF ,Sreenan S ,Hirano K , et al. Troglitazone action is independent of adipose tissue. J Clin Invest 1997;100:2900-2908
CrossRef | Web of Science | Medline36
Moitra J ,Mason MM ,Olive M , et al. Life without white fat: a transgenic mouse. Genes Dev 1998;12:3168-3181
CrossRef | Web of Science | Medline37
Shimomura I ,Hammer RE ,Richardson JA , et al. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 1998;12:3182-3194
CrossRef | Web of Science | Medline38
Unger RH . Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications. Diabetes 1995;44:863-870
CrossRef | Web of Science | Medline39
Unger RH ,Zhou YT ,Orci L . Regulation of fatty acid homeostasisin cells: novel role of leptin. Proc Natl Acad Sci U S A 1999;96:2327-2332
CrossRef | Web of Science | Medline40
Yamauchi T ,Kamon J ,Waki H , et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-946
CrossRef | Web of Science | Medline41
Fruebis J ,Tsao TS ,Javorschi S , et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 2001;98:2005-2010
CrossRef | Web of Science | Medline42
Berg AH ,Combs TP ,Du X ,Brownlee M ,Scherer PE . The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947-953
CrossRef | Web of Science | Medline
- Citing Articles (265)
Citing Articles
1
Martin G. Myers, Steven B. Heymsfield, Carol Haft, Barbara B. Kahn, Maren Laughlin, Rudolph L. Leibel, Matthias H. Tschöp, Jack A. Yanovski. (2012) Challenges and Opportunities of Defining Clinical Leptin Resistance. Cell Metabolism 15:2, 150-156
CrossRef2
Andreas Hillenbrand, Manfred Weiss, Uwe Knippschild, Anna Maria Wolf, Markus Huber-Lang. (2012) Sepsis-Induced Adipokine Change with regard to Insulin Resistance. International Journal of Inflammation 2012, 1-7
CrossRef3
Tusty-Jiuan Hsieh, Pei-Chen Hsieh, Ming-Tsang Wu, Wei-Chiao Chang, Pi-Jung Hsiao, Kun-Der Lin, Pong-Chun Chou, Shyi-Jang Shin. (2011) Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes. Cell Biology and Toxicology 27:6, 397-411
CrossRef4
Charmaine S Tam, Virgile Lecoultre, Eric Ravussin. (2011) Novel strategy for the use of leptin for obesity therapy. Expert Opinion on Biological Therapy 11:12, 1677-1685
CrossRef5
Guillaume Bidault, Camille Vatier, Jacqueline Capeau, Corinne Vigouroux, Véronique Béréziat. (2011) LMNA -linked lipodystrophies: from altered fat distribution to cellular alterations. Biochemical Society Transactions 39:6, 1752-1757
CrossRef6
J. Argente, J.F. Sotos. (2011) Hipercrecimientos con y sin obesidad: fundamentos clínicos y moleculares. Anales de Pediatría
CrossRef7
John I Gallin. (2011) The NIH Clinical Center and the future of clinical research. Nature Medicine 17:10, 1221-1223
CrossRef8
Warda Fatima, Adeela Shahid, Muhammad Imran, Jaida Manzoor, Shahida Hasnain, Sobia Rana, Saqib Mahmood. (2011) Leptin deficiency and leptin gene mutations in obese children from Pakistan. International Journal of Pediatric Obesity 6:5-6, 419-427
CrossRef9
Melissa K. Crocker, Jack A. Yanovski. (2011) Pediatric Obesity: Etiology and Treatment. Pediatric Clinics of North America 58:5, 1217-1240
CrossRef10
Michael J. Stuart, Bernhard T. Baune. (2011) Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neuroscience & Biobehavioral Reviews
CrossRef11
Todd T. Brown, Marshall J. Glesby. (2011) Management of the metabolic effects of HIV and HIV drugs. Nature Reviews Endocrinology
CrossRef12
Irina Kowalska, Monika Karczewska-Kupczewska, Marek Strączkowski. (2011) Adipocytokines, gut hormones and growth factors in anorexia nervosa. Clinica Chimica Acta 412:19-20, 1702-1711
CrossRef13
Jane M Johnston, Steven J Greco, Ashkan Hamzelou, J Wesson Ashford, Nikolaos Tezapsidis. (2011) Repositioning leptin as a therapy for Alzheimer’s disease. Therapy 8:5, 481-490
CrossRef14
Elif A Oral. (2011) Leptin for type 1 diabetes: coming onto stage to be (or not?). Pediatric Diabetesno-no
CrossRef15
B. P. Cummings, A. Bettaieb, J. L. Graham, K. L. Stanhope, R. Dill, G. J. Morton, F. G. Haj, P. J. Havel. (2011) Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats. Proceedings of the National Academy of Sciences 108:35, 14670-14675
CrossRef16
Alberto Chavez, Devjit Tripathy. 2011. Adipokines and Obesity. , 199-213.
CrossRef17
Suzanne L Quinn, M. Cecilia Lansang, Deanna Mina. (2011) Safety and Effectiveness of U-500 Insulin Therapy in Patients with Insulin-Resistant Type 2 Diabetes Mellitus. Pharmacotherapy 31:7, 695-702
CrossRef18
Laurent Gautron, Joel K. Elmquist. (2011) Sixteen years and counting: an update on leptin in energy balance. Journal of Clinical Investigation 121:6, 2087-2093
CrossRef19
Osamu Itani, Yoshitaka Kaneita, Atsushi Murata, Eise Yokoyama, Takashi Ohida. (2011) Association of onset of obesity with sleep duration and shift work among Japanese adults. Sleep Medicine 12:4, 341-345
CrossRef20
Joseph S. Marino, Yong Xu, Jennifer W. Hill. (2011) Central insulin and leptin-mediated autonomic control of glucose homeostasis. Trends in Endocrinology & Metabolism
CrossRef21
K. Miehle, M. Stumvoll, M. Fasshauer. (2011) Lipodystrophie. Der Internist 52:4, 362-373
CrossRef22
Amita Yadav, Pramila jyoti, S. K. Jain, Jayashree Bhattacharjee. (2011) Correlation of Adiponectin and Leptin with Insulin Resistance: A Pilot Study in Healthy North Indian Population. Indian Journal of Clinical Biochemistry 26:2, 193-196
CrossRef23
2011. References. , 283-360.
CrossRef24
Christina G. Fiorenza, Sharon H. Chou, Christos S. Mantzoros. (2011) Lipodystrophy: pathophysiology and advances in treatment. Nature Reviews Endocrinology 7:3, 137-150
CrossRef25
Placido Llaneza, Celestino González, José Fernandez-Iñarrea, Ana Alonso, Fernando Diaz, Ignacio Arnott, Javier Ferrer-Barriendos. (2011) Soy isoflavones, diet and physical exercise modify serum cytokines in healthy obese postmenopausal women. Phytomedicine 18:4, 245-250
CrossRef26
Noriyuki Ouchi, Jennifer L. Parker, Jesse J. Lugus, Kenneth Walsh. (2011) Adipokines in inflammation and metabolic disease. Nature Reviews Immunology 11:2, 85-97
CrossRef27
Lisa G. Rider, Carol B. Lindsley, James T. Cassidy. 2011. JUVENILE DERMATOMYOSITIS. , 375-413.
CrossRef28
Yasumichi Arai, Michiyo Takayama, Yukiko Abe, Nobuyoshi Hirose. (2011) Adipokines and Aging. Journal of Atherosclerosis and Thrombosis 18:7, 545-550
CrossRef29
Wei Luo, Peter F. Bodary, Yuechun Shen, Kevin J. Wickenheiser, Miina K. Öhman, Chiao Guo, Kristina L. Bahrou, Martin G. Myers, Daniel T. Eitzman. (2011) Leptin receptor-induced STAT3-independent signaling pathways are protective against atherosclerosis in a murine model of obesity and hyperlipidemia. Atherosclerosis 214:1, 81-85
CrossRef30
Jeffrey M. Friedman. (2011) Leptin and the Regulation of Body Weigh. The Keio Journal of Medicine 60:1, 1-9
CrossRef31
Aleksandra Rojek, Marek Niedziela. (2011) Insulin receptor and its relationship with different forms of insulin resistance. Advances in Cell Biology 1:-1, 1-32
CrossRef32
Carmine Zoccali, Francesca Mallamaci. (2011) Adiponectin and Leptin in Chronic Kidney Disease: Causal Factors or Mere Risk Markers?. Journal of Renal Nutrition 21:1, 87-91
CrossRef33
Hélène De Naeyer, D. Margriet Ouwens, Yves Van Nieuwenhove, Piet Pattyn, Leen M. ‘t Hart, Jean-Marc Kaufman, Henrike Sell, Juergen Eckel, Claude Cuvelier, Youri E. Taes, Johannes B. Ruige. (2011) Combined Gene and Protein Expression of Hormone-Sensitive Lipase and Adipose Triglyceride Lipase, Mitochondrial Content, and Adipocyte Size in Subcutaneous and Visceral Adipose Tissue of Morbidly Obese Men. Obesity Facts 4:5, 407-416
CrossRef34
Jean L. Chan, Karen Lutz, Elaine Cochran, Wenying Huang, Yvette Peters, Christian Weyer, Phillip Gorden. (2011) Clinical Effects of Long-Term Metreleptin Treatment in Patients with Lipodystrophy. Endocrine Practice 1:-1, 1-31
CrossRef35
Laura Scolaro, Marco Cassone, Jerzy W Kolaczynski, Laszlo Otvos Jr, Eva Surmacz. (2010) Leptin-based therapeutics. Expert Review of Endocrinology & Metabolism 5:6, 875-889
CrossRef36
Martin G. Myers, Rudolph L. Leibel, Randy J. Seeley, Michael W. Schwartz. (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends in Endocrinology & Metabolism 21:11, 643-651
CrossRef37
Yingfeng Deng, Philipp E. Scherer. (2010) Adipokines as novel biomarkers and regulators of the metabolic syndrome. Annals of the New York Academy of Sciences 1212:1, E1-E19
CrossRef38
T. Fujikawa, J.-C. Chuang, I. Sakata, G. Ramadori, R. Coppari. (2010) Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice. Proceedings of the National Academy of Sciences 107:40, 17391-17396
CrossRef39
Ushma S. Neill. (2010) Leaping for leptin: the 2010 Albert Lasker Basic Medical Research Award goes to Douglas Coleman and Jeffrey M. Friedman. Journal of Clinical Investigation 120:10, 3413-3418
CrossRef40
Konstantinos Lois, Georgios Valsamakis, Georgio Mastorakos, Sudhesh Kumar. (2010) The impact of insulin resistance on woman's health and potential treatment options. Annals of the New York Academy of Sciences 1205:1, 156-165
CrossRef41
P. Beijer, Th.A.M. Hurk, M.A.M.J. Vroede, R.J. Odink. (2010) Een zuigeling zonder subcutaan vet: berardinelli-seip-syndroom. Tijdschrift voor Kindergeneeskunde 2010:1, 33-36
CrossRef42
Henry Bohler, Sriprakash Mokshagundam, Stephen J. Winters. (2010) Adipose tissue and reproduction in women. Fertility and Sterility 94:3, 795-825
CrossRef43
Vladimír Teplan, František Vyhnánek, Robert Gürlich, Martin Haluzík, Jaroslav Racek, Ivana Vyhnankova, Milena Štollová, Vladimír Teplan. (2010) Increased proinflammatory cytokine production in adipose tissue of obese patients with chronic kidney disease. Wiener klinische Wochenschrift 122:15-16, 466-473
CrossRef44
Angus Jones, Andrew T. Hattersley. 2010. Monogenic Causes of Diabetes. , 243-264.
CrossRef45
Batya B Davidovici, Naveed Sattar, Prinz C Jörg, Luis Puig, Paul Emery, Jonathan N Barker, Peter van de Kerkhof, Mona Ståhle, Frank O Nestle, Giampiero Girolomoni, James G Krueger. (2010) Psoriasis and Systemic Inflammatory Diseases: Potential Mechanistic Links between Skin Disease and Co-Morbid Conditions. Journal of Investigative Dermatology 130:7, 1785-1796
CrossRef46
François R. Jornayvaz, Varman T. Samuel, Gerald I. Shulman. (2010) The Role of Muscle Insulin Resistance in the Pathogenesis of Atherogenic Dyslipidemia and Nonalcoholic Fatty Liver Disease Associated with the Metabolic Syndrome. Annual Review of Nutrition 30:1, 273-290
CrossRef47
Kanakadurga Singer, Massimo Pietropaolo, Ram K Menon. (2010) Improving type 1 diabetes control with leptin - Is this a game-changer?. Pediatric Diabetes 11:4, 216-217
CrossRef48
Roger H. Unger, Philipp E. Scherer. (2010) Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends in Endocrinology & Metabolism 21:6, 345-352
CrossRef49
Thien T. Tran, C. Ronald Kahn. (2010) Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nature Reviews Endocrinology 6:4, 195-213
CrossRef50
T Fuke, T Yoshizaki, M Kondo, K Morino, T Obata, S Ugi, Y Nishio, S Maeda, A Kashiwagi, H Maegawa. (2010) Transcription factor AP-2β inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes. International Journal of Obesity 34:4, 670-678
CrossRef51
James J. Lynch, Eugene W. Shek, Vincent Castagné, Scott W. Mittelstadt. (2010) The proconvulsant effects of leptin on glutamate receptor-mediated seizures in mice. Brain Research Bulletin 82:1-2, 99-103
CrossRef52
D. H. McGibbon. 2010. Subcutaneous Fat. , 1-49.
CrossRef53
M.-y. Wang, L. Chen, G. O. Clark, Y. Lee, R. D. Stevens, O. R. Ilkayeva, B. R. Wenner, J. R. Bain, M. J. Charron, C. B. Newgard, R. H. Unger. (2010) From the Cover: Feature Article: Leptin therapy in insulin-deficient type I diabetes. Proceedings of the National Academy of Sciences 107:11, 4813-4819
CrossRef54
Roger H. Unger, Gregory O. Clark, Philipp E. Scherer, Lelio Orci. (2010) Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1801:3, 209-214
CrossRef55
Jean L. Chan, Elif A. Oral. (2010) Clinical Classification and Treatment of Congenital and Acquired Lipodystrophy. Endocrine Practice 16:2, 310-323
CrossRef56
Elif A. Oral, Jean L. Chan. (2010) Rationale for Leptin-Replacement Therapy for Severe Lipodystrophy. Endocrine Practice 16:2, 324-333
CrossRef57
E J Bak, H G Park, J M Kim, J M Kim, Y-J Yoo, J-H Cha. (2010) Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes. International Journal of Obesity 34:2, 250-260
CrossRef58
Matthias Blüher. (2010) Do adipokines link obesity to its related metabolic and cardiovascular diseases?. Clinical Lipidology 5:1, 95-107
CrossRef59
L. Herrero, H. Shapiro, A. Nayer, J. Lee, S. E. Shoelson. (2010) Inflammation and adipose tissue macrophages in lipodystrophic mice. Proceedings of the National Academy of Sciences 107:1, 240-245
CrossRef60
Yoshimaro YANAGAWA, Tadashi MORIMURA, Katsuhiko TSUNEKAWA, Koji SEKI, Takayuki OGIWARA, Nobuo KOTAJIMA, Tetsuo MACHIDA, Shingo MATSUMOTO, Takumi ADACHI, Masami MURAKAMI. (2010) Oxidative Stress Associated with Rapid Weight Reduction Decreases Circulating Adiponectin Concentrations. Endocrine Journal 57:4, 339-345
CrossRef61
A. Y. Chong, B. C. Lupsa, E. K. Cochran, P. Gorden. (2010) Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia 53:1, 27-35
CrossRef62
Kristina Hedbacker, Kıvanç Birsoy, Robert W. Wysocki, Esra Asilmaz, Rexford S. Ahima, I. Sadaf Farooqi, Jeffrey M. Friedman. (2010) Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene. Cell Metabolism 11:1, 11-22
CrossRef63
D. B. Savage, S. O’Rahilly. (2010) Leptin therapy in lipodystrophy. Diabetologia 53:1, 7-9
CrossRef64
Zhaoxia Wang, Tomohiro Nakayama. (2010) Inflammation, a Link between Obesity and Cardiovascular Disease. Mediators of Inflammation 2010, 1-17
CrossRef65
Atsushi Nishiyama, Mariko Yagi, Hiroyuki Awano, Yo Okizuka, Taro Maeda, Shinsaku Yoshida, Yasuhiro Takeshima, Masafumi Matsuo. (2009) Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations. Pediatrics International 51:6, 775-779
CrossRef66
Sang Hoon Han, Bum Sik Chin, Han Sung Lee, Su Jin Jeong, Hee Kyoung Choi, Chang Oh Kim, Jun Yong Choi, Young Goo Song, Hyun Chul Lee, June Myung Kim. (2009) Serum retinol-binding protein 4 correlates with obesity, insulin resistance, and dyslipidemia in HIV-infected subjects receiving highly active antiretroviral therapy. Metabolism 58:11, 1523-1529
CrossRef67
Christopher Sinal, Kerry Goralski. 2009. Adipose Tissue as Endocrine Organ. , 23-45.
CrossRef68
Peter Zahradka, Carla Taylor, Vanessa DeClercq, Ryan Hunt, Maria Baranowski, Danielle Stringer. 2009. Inflammatory Actions of Adiponectin, Leptin, and Resistin. , 167-187.
CrossRef69
Kazuwa Nakao, Akihiro Yasoda, Ken Ebihara, Kiminori Hosoda, Masashi Mukoyama. (2009) Translational research of novel hormones: lessons from animal models and rare human diseases for common human diseases. Journal of Molecular Medicine 87:10, 1029-1039
CrossRef70
Satya P. Kalra. (2009) Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation. Peptides 30:10, 1957-1963
CrossRef71
Alexander R. Moschen, Clemens Molnar, Anna Maria Wolf, Helmut Weiss, Ivo Graziadei, Susanne Kaser, Christoph F. Ebenbichler, Sylvia Stadlmann, Patrizia L. Moser, Herbert Tilg. (2009) Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. Journal of Hepatology 51:4, 765-777
CrossRef72
Geoffrey C Farrell. (2009) The liver and the waistline: Fifty years of growth. Journal of Gastroenterology and Hepatology 24, S105-S118
CrossRef73
Eric Ravussin, Steven R. Smith, Julie A. Mitchell, Reshma Shringarpure, Kevin Shan, Holly Maier, Joy E. Koda, Christian Weyer. (2009) Enhanced Weight Loss With Pramlintide/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy. Obesity 17:9, 1736-1743
CrossRef74
Melissa K. Crocker, Jack A. Yanovski. (2009) Pediatric Obesity: Etiology and Treatment. Endocrinology & Metabolism Clinics of North America 38:3, 525-548
CrossRef75
Biao Wang, Jun Zhu, Khalid Mounzih, Eric F. Chehab, Yaohuang Ke, Farid F. Chehab. (2009) Overexpression of the transcription factor foxo4 is associated with rapid glucose clearance. Molecular and Cellular Endocrinology 307:1-2, 217-223
CrossRef76
M J Müller, A Bosy-Westphal, W Later, V Haas, M Heller. (2009) Functional body composition: insights into the regulation of energy metabolism and some clinical applications. European Journal of Clinical Nutrition 63:9, 1045-1056
CrossRef77
Vinaya Simha, Abhimanyu Garg. (2009) Inherited lipodystrophies and hypertriglyceridemia. Current Opinion in Lipidology 20:4, 300-308
CrossRef78
Tomas Roubicek, Marketa Bartlova, Jana Krajickova, Denisa Haluzikova, Milos Mraz, Zdena Lacinova, Michal Kudla, Vladimir Teplan, Martin Haluzik. (2009) Increased production of proinflammatory cytokines in adipose tissue of patients with end-stage renal disease. Nutrition 25:7-8, 762-768
CrossRef79
J.-F. Dumas, G. Simard, M. Flamment, P.-H. Ducluzeau, P. Ritz. (2009) Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?. Diabetes & Metabolism 35:3, 159-167
CrossRef80
T. Kusakabe, H. Tanioka, K. Ebihara, M. Hirata, L. Miyamoto, F. Miyanaga, H. Hige, D. Aotani, T. Fujisawa, H. Masuzaki, K. Hosoda, K. Nakao. (2009) Beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat diet. Diabetologia 52:4, 675-683
CrossRef81
Karina Braga Gomes, Victor Cavalcanti Pardini, Ana Paula Fernandes. (2009) Clinical and molecular aspects of Berardinelli–Seip Congenital Lipodystrophy (BSCL). Clinica Chimica Acta 402:1-2, 1-6
CrossRef82
Ivona Brasnjevic, Harry W.M. Steinbusch, Christoph Schmitz, Pilar Martinez-Martinez. (2009) Delivery of peptide and protein drugs over the blood–brain barrier. Progress in Neurobiology 87:4, 212-251
CrossRef83
Eugenia Negredo, Jordi Puig, David Aldea, Manuel Medina, Carla Estany, Núria Pérez-Álvarez, Carmina Rodríguez-Fumaz, Jose A. Muñoz-Moreno, Carmen Higueras, Vicente Gonzalez-Mestre, Bonaventura Clotet. (2009) Four-Year Safety with Polyacrylamide Hydrogel to Correct Antiretroviral-Related Facial Lipoatrophy. AIDS Research and Human Retroviruses 25:4, 451-455
CrossRef84
F. A. J. L. Scheer, M. F. Hilton, C. S. Mantzoros, S. A. Shea. (2009) From the Cover: Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences 106:11, 4453-4458
CrossRef85
Martin G. Myers, Heike Münzberg, Gina M. Leinninger, Rebecca L. Leshan. (2009) The Geometry of Leptin Action in the Brain: More Complicated Than a Simple ARC. Cell Metabolism 9:2, 117-123
CrossRef86
Paolo Calabrò, Enrica Golia, Valeria Maddaloni, Marco Malvezzi, Beniamino Casillo, Carla Marotta, Raffaele Calabrò, Paolo Golino. (2009) Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease?. Internal and Emergency Medicine 4:1, 25-34
CrossRef87
Melissa A. Lawson. (2009) Lipoatrophic Diabetes: A Case Report with a Brief Review of the Literature. Journal of Adolescent Health 44:1, 94-95
CrossRef88
R H Eckel. (2008) Obesity research in the next decade. International Journal of Obesity 32, S143-S151
CrossRef89
Nicole C Kesty, Jonathan D Roth, David Maggs. (2008) Hormone-based therapies in the regulation of fuel metabolism and body weight. Expert Opinion on Biological Therapy 8:11, 1733-1747
CrossRef90
Y. Arai, M. Takayama, Y. Gondo, H. Inagaki, K. Yamamura, S. Nakazawa, T. Kojima, Y. Ebihara, K. Shimizu, Y. Masui, K. Kitagawa, T. Takebayashi, N. Hirose. (2008) Adipose Endocrine Function, Insulin-Like Growth Factor-1 Axis, and Exceptional Survival Beyond 100 Years of Age. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:11, 1209-1218
CrossRef91
Seth S. Martin, Atif Qasim, Muredach P. Reilly. (2008) Leptin Resistance. Journal of the American College of Cardiology 52:15, 1201-1210
CrossRef92
X. Yu, B.-H. Park, M.-Y. Wang, Z. V. Wang, R. H. Unger. (2008) Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proceedings of the National Academy of Sciences 105:37, 14070-14075
CrossRef93
R. H. Unger. (2008) Noninvasive tracking of gene expression by reporter transgene imaging. Proceedings of the National Academy of Sciences 105:35, 12641-12642
CrossRef94
Yo Hotta, Hiroshi Yatsuya, Hideaki Toyoshima, Kunihiro Matsushita, Hirotsugu Mitsuhashi, Seiko Takefuji, Yutaka Oiso, Koji Tamakoshi. (2008) Low leptin but high insulin resistance of smokers in Japanese men. Diabetes Research and Clinical Practice 81:3, 358-364
CrossRef95
Belinda J. Yauger, Phillip Gorden, Jean Park, Elaine Cochran, Pamela Stratton. (2008) Effect of Depot Medroxyprogesterone Acetate on Glucose Tolerance in Generalized Lipodystrophy. Obstetrics & Gynecology 112:2, Part 2, 445-447
CrossRef96
Sasha Taleban, Heather T. Carew, Helén L. Dichek, Samir S. Deeb, David Hollenback, David S. Weigle, David E. Cummings, John D. Brunzell. (2008) Energy balance in congenital generalized lipodystrophy type I. Metabolism 57:8, 1155-1161
CrossRef97
Hansjoerg Heep,, Christian Wedemeyer,, Jie Xu,, Sebastian Hofmeister,, Marius von Knoch,. (2008) No Adaptations in Bone of Leptin-Deficient ob/ob Mice in Response to Loading. BIOmaterialien 9:1-2, 18-25
CrossRef98
J. E. Mallewa, E. Wilkins, J. Vilar, M. Mallewa, D. Doran, D. Back, M. Pirmohamed. (2008) HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options. Journal of Antimicrobial Chemotherapy 62:4, 648-660
CrossRef99
Rexford S. Ahima. (2008) Revisiting leptin’s role in obesity and weight loss. Journal of Clinical Investigation
CrossRef100
Funda Kosova, Aylin Sepici-Dincel, Atilla Engin, Leyla Memiş, Cemile Koca, Nilgün Altan. (2008) The thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats. Endocrine 33:3, 317-322
CrossRef101
Sarah N Oosman, Ada W Lam, George Harb, Suraj Unniappan, Ni T Lam, Travis Webber, Daniel Bruch, Qiu-Xia Zhang, Gregory S Korbutt, Timothy J Kieffer. (2008) Treatment of Obesity and Diabetes in Mice by Transplant of Gut Cells Engineered to Produce Leptin. Molecular Therapy 16:6, 1138-1145
CrossRef102
Jeong Soon Lee, Jae Myoung Suh, Hong Gyu Park, Eun Jung Bak, Yun-Jung Yoo, Jeong-Heon Cha. (2008) Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages. Differentiation 76:5, 478-487
CrossRef103
J. D. Roth, B. L. Roland, R. L. Cole, J. L. Trevaskis, C. Weyer, J. E. Koda, C. M. Anderson, D. G. Parkes, A. D. Baron. (2008) Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies. Proceedings of the National Academy of Sciences 105:20, 7257-7262
CrossRef104
Adilson Guilherme, Joseph V. Virbasius, Vishwajeet Puri, Michael P. Czech. (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nature Reviews Molecular Cell Biology 9:5, 367-377
CrossRef105
Silvie Timmers, Patrick Schrauwen, Johan de Vogel. (2008) Muscular diacylglycerol metabolism and insulin resistance. Physiology & Behavior 94:2, 242-251
CrossRef106
Paolo Calabrò, Giuseppe Limongelli, Giuseppe Pacileo, Giovanni Di Salvo, Paolo Golino, Raffaele Calabrò. (2008) The role of adiposity as a determinant of an inflammatory milieu. Journal of Cardiovascular Medicine 9:5, 450-460
CrossRef107
M. Karmazyn, D. M. Purdham, V. Rajapurohitam, A. Zeidan. (2008) Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart. Cardiovascular Research 79:2, 279-286
CrossRef108
Jean-Marc Guettier, Jean Y. Park, Elaine K. Cochran, Christine Poitou, Arnaud Basdevant, Muriel Meier, Karine Clément, Jocelyne Magré, Phillip Gorden. (2008) Leptin therapy for partial lipodystrophy linked to a PPAR-γ mutation. Clinical Endocrinology 68:4, 547-554
CrossRef109
Bor Luen Tang. (2008) Leptin as a neuroprotective agent. Biochemical and Biophysical Research Communications 368:2, 181-185
CrossRef110
Deborah M. Muoio, Christopher B. Newgard. (2008) Mechanisms of disease: Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nature Reviews Molecular Cell Biology 9:3, 193-205
CrossRef111
Paolo Calabro, Edward T. H. Yeh. (2008) Intra-abdominal adiposity, inflammation, and cardiovascular risk: New insight into global cardiometabolic risk. Current Hypertension Reports 10:1, 32-38
CrossRef112
Jie Dong, Naoki Ishimori, Beverly Paigen, Hiroyuki Tsutsui, Satoshi Fujii. (2008) Role of modulator recognition factor 2 in adipogenesis and leptin expression in 3T3-L1 cells. Biochemical and Biophysical Research Communications 366:2, 551-555
CrossRef113
B. Antuna-Puente, B. Feve, S. Fellahi, J.-P. Bastard. (2008) Adipokines: The missing link between insulin resistance and obesity. Diabetes & Metabolism 34:1, 2-11
CrossRef114
Fabrizio Montecucco, Sabine Steffens, François Mach. (2008) Insulin Resistance: A Proinflammatory State Mediated by Lipid-Induced Signaling Dysfunction and Involved in Atherosclerotic Plaque Instability. Mediators of Inflammation 2008, 1-10
CrossRef115
Alexandra Scholze, Martin Tepel. (2007) CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Role of Leptin in Reverse Epidemiology in Chronic Kidney Disease. Seminars in Dialysis 20:6, 534-538
CrossRef116
James L. Trevaskis, Barbara Gawronska-Kozak, Gregory M. Sutton, Michele McNeil, Jacqueline M. Stephens, Steven R. Smith, Andrew A. Butler. (2007) Role of Adiponectin and Inflammation in Insulin Resistance of Mc3r and Mc4r Knockout Mice**. Obesity 15:11, 2664-2672
CrossRef117
George A. Bray. (2007) Medical Therapy for Obesity—Current Status and Future Hopes. Medical Clinics of North America 91:6, 1225-1253
CrossRef118
Gwendolyn W. Louis, Martin G. Myers. (2007) The role of leptin in the regulation of neuroendocrine function and CNS development. Reviews in Endocrine and Metabolic Disorders 8:2, 85-94
CrossRef119
Yuko Kobashi, Amy Schoenbaum, Robert P. Hasserjian, Daniel I. Rosenthal. (2007) Berardinelli-Seip lipodystrophy. Skeletal Radiology 36:10, 999-1003
CrossRef120
Houshang Monajemi, Erik Stroes, Robert A. Hegele, Eric Fliers. (2007) Inherited lipodystrophies and the metabolic syndrome. Clinical Endocrinology 0:0, 070611020455003-???
CrossRef121
Alexandra Scholze, Dirk Rattensperger, Walter Zidek, Martin Tepel. (2007) Low Serum Leptin Predicts Mortality in Patients with Chronic Kidney Disease Stage 5*. Obesity 15:6, 1617-1622
CrossRef122
E. Chang, R. Sekhar, S. Patel, A. Balasubramanyam. (2007) Dysregulated Energy Expenditure in HIV-Infected Patients: A Mechanistic Review. Clinical Infectious Diseases 44:11, 1509-1517
CrossRef123
Kamyar Kalantar-Zadeh. (2007) So, Is Leptin Good or Bad in Chronic Kidney Disease?. Obesity 15:6, 1343-1344
CrossRef124
Li Liu, Yiying Zhang, Nancy Chen, Xiaojing Shi, Bonny Tsang, Yi-Hao Yu. (2007) Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. Journal of Clinical Investigation 117:6, 1679-1689
CrossRef125
A. M. Brennan, T. Y. Li, I. Kelesidis, A. Gavrila, F. B. Hu, C. S. Mantzoros. (2007) Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study. Diabetologia 50:6, 1178-1185
CrossRef126
Tomohiro Tanaka, Hiroaki Masuzaki, Shintaro Yasue, Ken Ebihara, Tetsuya Shiuchi, Takako Ishii, Naoki Arai, Masakazu Hirata, Hiroshi Yamamoto, Tatsuya Hayashi, Kiminori Hosoda, Yasuhiko Minokoshi, Kazuwa Nakao. (2007) Central Melanocortin Signaling Restores Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation in Mice Fed a High-Fat Diet. Cell Metabolism 5:5, 395-402
CrossRef127
Laura L Sweeney, Aoife M Brennan, Christos S Mantzoros. (2007) The role of adipokines in relation to HIV lipodystrophy. AIDS 21:8, 895-904
CrossRef128
Anthony P. Coll, I. Sadaf Farooqi, Stephen O'Rahilly. (2007) The Hormonal Control of Food Intake. Cell 129:2, 251-262
CrossRef129
Jean Y. Park, Edward D. Javor, Elaine K. Cochran, Alex M. DePaoli, Phillip Gorden. (2007) Long-term efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy. Metabolism 56:4, 508-516
CrossRef130
Karine Lolmède, Cyrile Curat, Anne Bouloumié, Alexandra Miranville, Coralie Sengenès. 2007. Leptin as a Vasoactive Adipokine. , 93-103.
CrossRef131
Hironori Waki, Peter Tontonoz. (2007) Endocrine Functions of Adipose Tissue. Annual Review of Pathology: Mechanisms of Disease 2:1, 31-56
CrossRef132
Eve A. Roberts. (2007) Non-alcoholic Steatohepatitis in Children. Clinics in Liver Disease 11:1, 155-172
CrossRef133
Lisa A. Kosmiski, Daniel H. Bessesen, Sarah A. Stotz, John R. Koeppe, Tracy J. Horton. (2007) Short-term energy restriction reduces resting energy expenditure in patients with HIV lipodystrophy and hypermetabolism. Metabolism 56:2, 289-295
CrossRef134
Paolo Calabro, Edward T. H. Yeh. (2007) Intra-abdominal adiposity, inflammation, and cardiovascular risk: New insight in the global cardiometabolic risk. Current Cardiovascular Risk Reports 1:1, 32-38
CrossRef135
Milagros Gloria Huerta. (2007) Adiponectin and leptin: Potential tools in the differential diagnosis of pediatric diabetes?. Reviews in Endocrine and Metabolic Disorders 7:3, 187-196
CrossRef136
Fabio Marra. (2007) Leptin and liver tissue repair: Do rodent models provide the answers?. Journal of Hepatology 46:1, 12-18
CrossRef137
Lübeck Ralf Paus, J. Klein, P. A. Permana, M. Owecki, G. N. Chaldakov, M. Böhm, G. Hausman, C. M. Lapière, P. Atanassova, J. Sowiński, M. Fasshauer, D. B. Hausman, E. Maquoi, A. B. Tonchev, V. N. Peneva, K. P. Vlachanov, M. Fiore, L. Aloe, A. Slominski, C. L. Reardon, T. J. Ryan, C. M. Pond. (2007) What are subcutaneous adipocytes really good for…?. Experimental Dermatology 16:1, 45-70
CrossRef138
George Yuan, Robert A. Hegele. (2007) Genetic Forms of the Cardiometabolic Syndrome: What Can They Tell the Clinician?. Journal of the CardioMetabolic Syndrome 2:1, 45-48
CrossRef139
Kerry B. Goralski, Christopher J. Sinal. (2007) Type 2 diabetes and cardiovascular disease: getting to the fat of the matterThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.. Canadian Journal of Physiology and Pharmacology 85:1, 113-132
CrossRef140
Ralf Paus, Johannes Klein, Mathias Fasshauer. (2007) Viewpoint 1. Experimental Dermatology 16:1, 50-53
CrossRef141
Neda Rasouli, Behzad Molavi, Steven C. Elbein, Philip A. Kern. (2007) Ectopic fat accumulation and metabolic syndrome. Diabetes, Obesity and Metabolism 9:1, 1-10
CrossRef142
Yong-Woon Kim. (2007) Leptin Resistance. Journal of Korean Endocrine Society 22:5, 311
CrossRef143
Barbara Mlinar, Janja Marc, Andrej Janež, Marija Pfeifer. (2007) Molecular mechanisms of insulin resistance and associated diseases. Clinica Chimica Acta 375:1-2, 20-35
CrossRef144
Evan D. Rosen, Bruce M. Spiegelman. (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444:7121, 847-853
CrossRef145
Harold Bays, Lawrence Blonde, Robert Rosenson. (2006) Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?. Expert Review of Cardiovascular Therapy 4:6, 871-895
CrossRef146
Marcelo L. G. Correia, Kamal Rahmouni. (2006) Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes, Obesity and Metabolism 8:6, 603-610
CrossRef147
F. Dressler, H.-I. Huppertz. (2006) Juvenile Dermatomyositis. Zeitschrift für Rheumatologie 65:7, 587-594
CrossRef148
Nahum Méndez-Sánchez, Norberto C. Chávez-Tapia, Roberto Medina-Santillán, Antonio R. Villa, Karla Sánchez-Lara, Guadalupe Ponciano-Rodríguez, Martha H. Ramos, Misael Uribe. (2006) The Efficacy of Adipokines and Indices of Metabolic Syndrome as Predictors of Severe Obesity-Related Hepatic Steatosis. Digestive Diseases and Sciences 51:10, 1716-1722
CrossRef149
Kinan Rifai, Stephan C. Bischoff, Adji Widjaja, Georg Brabant, Michael P. Manns, Johann Ockenga. (2006) Leptin and insulin response to long-term total parenteral nutrition depends on body fat mass. Clinical Nutrition 25:5, 773-779
CrossRef150
Jacqueline Capeau, Jocelyne Magré, Martine Caron, Claire Lagathu, Jean-Philippe Bastard, Corinne Vigouroux. (2006) Genetic and acquired lipodystrophies: from fat redistribution to insulin resistance and aging. Future Lipidology 1:5, 593-604
CrossRef151
Dominic S. Ng. 2006. Insulin Resistance, Diabetes and its Complications. .
CrossRef152
Allyn L Mark. (2006) DIETARY THERAPY FOR OBESITY IS A FAILURE AND PHARMACOTHERAPY IS THE FUTURE: A POINT OF VIEW. Clinical and Experimental Pharmacology and Physiology 33:9, 857-862
CrossRef153
Anil K. Agarwal, Abhimanyu Garg. (2006) Genetic Disorders of Adipose Tissue Development, Differentiation, and Death. Annual Review of Genomics and Human Genetics 7:1, 175-199
CrossRef154
S. Starcke, G. Vollmer. (2006) Is there an estrogenic component in the metabolic syndrome?. Genes & Nutrition 1:3-4, 177-188
CrossRef155
Michael J. Wolfgang, M. Daniel Lane. (2006) Control of Energy Homeostasis: Role of Enzymes and Intermediates of Fatty Acid Metabolism in the Central Nervous System. Annual Review of Nutrition 26:1, 23-44
CrossRef156
Harold Bays, Christie Ballantyne. (2006) Adiposopathy: why do adiposity and obesity cause metabolic disease?. Future Lipidology 1:4, 389-420
CrossRef157
J CAPEAU, C VIGOUROUX, J MAGRE, O LASCOLS, M CARON, J BASTARD. (2006) Les syndromes lipodystrophiques : des adipopathies congénitales ou acquises. Comptes Rendus Biologies 329:8, 639-652
CrossRef158
RASA VERKAUSKIENE, CATHERINE DOLLFUS, MARTINE LEVINE, ALBERT FAYE, SAMIA DEGHMOUN, MURIEL HOUANG, DIDIER CHEVENNE, JEAN-LOUIS BRESSON, ST??PHANE BLANCHE, CLAIRE L??VY-MARCHAL. (2006) Serum Adiponectin and Leptin Concentrations in HIV-Infected Children with Fat Redistribution Syndrome. Pediatric Research 60:2, 225-230
CrossRef159
Vicente Estrada, María Teresa Martínez-Larrad, José Luis González-Sánchez, Noemí G.P. de Villar, Carina Zabena, Cristina Fernández, Manuel Serrano-Ríos. (2006) Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy. Metabolism 55:7, 940-945
CrossRef160
Karen Reue, Jack Phan. (2006) Metabolic consequences of lipodystrophy in mouse models. Current Opinion in Clinical Nutrition and Metabolic Care 9:4, 436-441
CrossRef161
Aoife M Brennan, Christos S Mantzoros. (2006) Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications. Nature Clinical Practice Endocrinology & Metabolism 2:6, 318-327
CrossRef162
Deborah M. Muoio, Christopher B. Newgard. (2006) Obesity-Related Derangements in Metabolic Regulation. Annual Review of Biochemistry 75:1, 367-401
CrossRef163
William A. Banks, Susan A. Farr, John E. Morley. (2006) The effects of high fat diets on the blood–brain barrier transport of leptin: Failure or adaptation?. Physiology & Behavior 88:3, 244-248
CrossRef164
Giovanna Demuro, Silvana Obici. (2006) Central nervous system and control of endogenous glucose production. Current Diabetes Reports 6:3, 188-193
CrossRef165
Yu-Feng Zhao, Dan Dan Feng, Chen Chen. (2006) Contribution of adipocyte-derived factors to beta-cell dysfunction in diabetes. The International Journal of Biochemistry & Cell Biology 38:5-6, 804-819
CrossRef166
Bulent O. Yildiz, Ibrahim C. Haznedaroglu. (2006) Rethinking leptin and insulin action: Therapeutic opportunities for diabetes. The International Journal of Biochemistry & Cell Biology 38:5-6, 820-830
CrossRef167
Frank Peelman, Cyril Couturier, Julie Dam, Lennart Zabeau, Jan Tavernier, Ralf Jockers. (2006) Techniques: New pharmacological perspectives for the leptin receptor. Trends in Pharmacological Sciences 27:4, 218-225
CrossRef168
Gerard Sáenz de Navarrete, Jordi Mesa, Albert Lecube. (2006) Lipodistrofia parcial familiar, variedad de Dunnigan: alteración fenotípica unida a síndrome metabólico. Medicina Clínica 126:15, 597-598
CrossRef169
Vinaya Simha, Abhimanyu Garg. (2006) Lipodystrophy: lessons in lipid and energy metabolism. Current Opinion in Lipidology 17:2, 162-169
CrossRef170
M. Montes De Oca Arjona, R. Pérez-Cano, R. Garcia-Juárez, A. Martín-Aspas, C. Fernández Gutiérrez Del Álamo, J.A. Girón-González. (2006) Structured Intermittent Interruption of Chronic HIV Infection Treatment with Highly Active Antiretroviral Therapy: Effects on Leptin and TNF- α. AIDS Research and Human Retroviruses 22:4, 307-314
CrossRef171
M. Michael Cohen. (2006) Role of leptin in regulating appetite, neuroendocrine function, and bone remodeling. American Journal of Medical Genetics Part A 140A:5, 515-524
CrossRef172
Rexford S. Ahima. (2006) Metabolic Actions of Adipocyte Hormones: Focus on Adiponectin. Obesity 14:2S, 9S-15S
CrossRef173
Anil K. Agarwal, Abhimanyu Garg. (2006) Genetic Basis of Lipodystrophies and Management of Metabolic Complications. Annual Review of Medicine 57:1, 297-311
CrossRef174
Gen-Sheng Feng. (2006) Shp2 as a therapeutic target for leptin resistance and obesity. Expert Opinion on Therapeutic Targets 10:1, 135-142
CrossRef175
Mari SATOH, Atsuko YOSHIZAWA, Masarou TAKESUE, Tsutomu SAJI, Susumu YOKOYA. (2006) Long-term Effects of Recombinant Human Insulin-like Growth Factor I Treatment on Glucose and Lipid Metabolism and the Growth of a Patient with Congenital Generalized Lipodystrophy. Endocrine Journal 53:5, 639-645
CrossRef176
Phillip Gorden, Jean Y. Park. (2006) The clinical efficacy of the adipocyte-derived hormone leptin in metabolic dysfunction*. Archives Of Physiology And Biochemistry 112:2, 114-118
CrossRef177
Johannes Klein, Nina Perwitz, Daniel Kraus, Mathias Fasshauer. (2006) Adipose tissue as source and target for novel therapies. Trends in Endocrinology & Metabolism 17:1, 26-32
CrossRef178
Iosif Kelesidis, Christos S. Mantzoros. (2006) Leptin and Its Emerging Role in Children and Adolescents. Clinical Pediatric Endocrinology 15:1, 1-14
CrossRef179
Joel K. Elmquist, Roberto Coppari, Nina Balthasar, Masumi Ichinose, Bradford B. Lowell. (2005) Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. The Journal of Comparative Neurology 493:1, 63-71
CrossRef180
Stergios J Moschos, Christos S Mantzoros. (2005) The emerging clinical significance of leptin in humans with absolute or relative leptin deficiency. Current Opinion in Internal Medicine 4:6, 596-601
CrossRef181
B Donadille, O Lascols, J Capeau, C Vigouroux. (2005) Etiological investigations in apparent type 2 diabetes: when to search for lamin A/C mutations?. Diabetes & Metabolism 31:6, 527-532
CrossRef182
Gregory J. Morton, Richard W. Gelling, Kevin D. Niswender, Christopher D. Morrison, Christopher J. Rhodes, Michael W. Schwartz. (2005) Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metabolism 2:6, 411-420
CrossRef183
Louise Hutley, Johannes B. Prins. (2005) Fat as an Endocrine Organ: Relationship to the Metabolic Syndrome. The American Journal of the Medical Sciences 330:6, 280-289
CrossRef184
K. B. Gomes, V. Cavalcanti Pardini, A. Clayton de Souza Ferreira, A. P. Fernandes. (2005) Phenotypic heterogeneity in biochemical parameters correlates with mutations in AGPAT2 or Seipin genes among Berardinelli–Seip congenital lipodystrophy patients. Journal of Inherited Metabolic Disease 28:6, 1123-1131
CrossRef185
Samuel Dagogo-Jack. 2005. Neuroendocrine Regulation of Food Intake. , 5-25.
CrossRef186
Jonas Burén, Jan W. Eriksson. (2005) Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?. Diabetes/Metabolism Research and Reviews 21:6, 487-494
CrossRef187
Dorothea Wunder, Nick A Bersinger, Christoph Fux, Rainer Weber, Enos Bernasconi, Matthias Cavassini, Heiner C Bucher, Veronique Schiffer, Patrick Schmid, Hansjakob Furrer. (2005) Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy. AIDS 19:16, 1837-1842
CrossRef188
C. BROBERGER. (2005) Brain regulation of food intake and appetite: molecules and networks. Journal of Internal Medicine 258:4, 301-327
CrossRef189
Andrea R. Nawrocki, Philipp E. Scherer. (2005) Keynote review: The adipocyte as a drug discovery target. Drug Discovery Today 10:18, 1219-1230
CrossRef190
Donald A. Williamson, Eric Ravussin, Ma-Li Wong, A. Wagner, A. DiPaoli, Sinan Caglayan, Metin Ozata, Corby Martin, Heather Walden, Cheryl Arnett, Julio Licinio. (2005) Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 45:1, 75-80
CrossRef191
Fabienne Foufelle, Pascal Ferré. (2005) Role of adenosine monophosphate-activated protein kinase in the control of energy homeostasis. Current Opinion in Clinical Nutrition and Metabolic Care 8:4, 355-360
CrossRef192
Carla Musso, Thomas Shawker, Elaine Cochran, Edward D. Javor, Janice Young, Phillip Gorden. (2005) Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth. Clinical Endocrinology 63:1, 73-78
CrossRef193
Hasan Askari, Jianmei Liu, Samuel Dagogo-Jack. (2005) Energy adaptation to glucocorticoid-induced hyperleptinemia in human beings. Metabolism 54:7, 876-880
CrossRef194
Jörg Dötsch, Kai Nüsken, Michael Schroth, Wolfgang Rascher, Udo Meißner. (2005) Alterations of leptin and ghrelin serum concentrations in renal disease: simple epiphenomena?. Pediatric Nephrology 20:6, 701-706
CrossRef195
Susan Kralisch, Johannes Klein, Matthias Bluher, Ralf Paschke, Michael Stumvoll, Mathias Fasshauer. (2005) Therapeutic perspectives of adipocytokines. Expert Opinion on Pharmacotherapy 6:6, 863-872
CrossRef196
S. Schinner, W. A. Scherbaum, S. R. Bornstein, A. Barthel. (2005) Molecular mechanisms of insulin resistance. Diabetic Medicine 22:6, 674-682
CrossRef197
Heike Münzberg, Martin G Myers. (2005) Molecular and anatomical determinants of central leptin resistance. Nature Neuroscience 8:5, 566-570
CrossRef198
Peter J. Havel. (2005) Dietary Fructose: Implications for Dysregulation of Energy Homeostasis and Lipid/Carbohydrate Metabolism. Nutrition Reviews 63:5, 133-157
CrossRef199
Edward D. Javor, Marc G. Ghany, Elaine K. Cochran, Elif Arioglu Oral, Alex M. DePaoli, Ahalya Premkumar, David E. Kleiner, Phillip Gorden. (2005) Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology 41:4, 753-760
CrossRef200
P. Cettour-Rose, C. Theander-Carrillo, C. Asensio, M. Klein, T. J. Visser, A. G. Burger, C. A. Meier, F. Rohner-Jeanrenaud. (2005) Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 48:4, 624-633
CrossRef201
Sarah H. Bates, Rohit N. Kulkarni, Matthew Seifert, Martin G. Myers. (2005) Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metabolism 1:3, 169-178
CrossRef202
Piero Portincasa, Ignazio Grattagliano, Vincenzo O. Palmieri, Giuseppe Palasciano. (2005) Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management. Clinical Biochemistry 38:3, 203-217
CrossRef203
Keith N. Frayn. (2005) Obesity and metabolic disease: is adipose tissue the culprit?. Proceedings of the Nutrition Society 64:01, 7-13
CrossRef204
Carla Musso, Elaine Cochran, Edward Javor, Janice Young, Alex M. DePaoli, Phillip Gorden. (2005) The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. Metabolism 54:2, 255-263
CrossRef205
Mehtap Cakir, Ramazan Sari, Ozgur Tosun, Umit Karayalcin. (2005) Leptin Response to Oral Glucose Tolerance Test in Obese and Nonobese Premenopausal Women. Endocrine Research 31:1, 1-8
CrossRef206
Roger H. Unger. (2005) Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie 87:1, 57-64
CrossRef207
Chris J Hukshorn, Wim HM Saris. (2004) Leptin and energy expenditure. Current Opinion in Clinical Nutrition and Metabolic Care 7:6, 629-633
CrossRef208
Roger H Unger. (2004) How adipocytes integrate surplus caloric intake with caloric storage: lessons from Morgan Spurlock and some French geese. Current Opinion in Endocrinology & Diabetes 11:5, 251-257
CrossRef209
Bernardo L. Wajchenberg, Rosangela F. Amancio, Ana T. Santomauro, Raul C. Maranhao. (2004) Metabolism of chylomicrons in patients with congenital lipoatrophic diabetes: a study with emulsion models of chylomicrons. Clinical Endocrinology 61:3, 347-352
CrossRef210
Koutaro Yokote, Satoshi Honjo, Kazuki Kobayashi, Masaki Fujimoto, Harukiyo Kawamura, Seijiro Mori, Yasushi Saito. (2004) METABOLIC IMPROVEMENT AND ABDOMINAL FAT REDISTRIBUTION IN WERNER SYNDROME BY PIOGLITAZONE. Journal of the American Geriatrics Society 52:9, 1582-1583
CrossRef211
Volker Ott, Mathias Fasshauer, Britta Meier, Andreas Dalski, Daniel Kraus, Thomas W. Gettys, Nina Perwitz, Johannes Klein. (2004) Ciliary neurotrophic factor influences endocrine adipocyte function: inhibition of leptin via PI 3-kinase. Molecular and Cellular Endocrinology 224:1-2, 21-27
CrossRef212
Ebihara, Ken, Masuzaki, Hiroaki, Nakao, Kazuwa, . (2004) Long-Term Leptin-Replacement Therapy for Lipoatrophic Diabetes. New England Journal of Medicine 351:6, 615-616
Full Text213
Carla Musso, Elaine Cochran, Stephanie Ann Moran, Monica C. Skarulis, Elif Arioglu Oral, Simeon Taylor, Phillip Gorden. (2004) Clinical Course of Genetic Diseases of the Insulin Receptor (Type A and Rabson-Mendenhall Syndromes). Medicine 83:4, 209-222
CrossRef214
Abhimanyu Garg, Anoop Misra. (2004) Lipodystrophies: rare disorders causing metabolic syndrome. Endocrinology & Metabolism Clinics of North America 33:2, 305-331
CrossRef215
Jeffrey M Friedman. (2004) Modern science versus the stigma of obesity. Nature Medicine 10:6, 563-569
CrossRef216
Shamina M Rangwala, Mitchell A Lazar. (2004) Peroxisome proliferator-activated receptor γ in diabetes and metabolism. Trends in Pharmacological Sciences 25:6, 331-336
CrossRef217
Akiko Takahashi-Yasuno, Hiroaki Masuzaki, Takashi Miyawaki, Naoki Matsuoka, Yoshihiro Ogawa, Tatsuya Hayashi, Kiminori Hosoda, Yasunao Yoshimasa, Gen Inoue, Kazuwa Nakao. (2004) Association of Ob-R gene polymorphism and insulin resistance in Japanese men. Metabolism 53:5, 650-654
CrossRef218
Rexford S Ahima, Suzette Y Osei. (2004) Leptin signaling. Physiology & Behavior 81:2, 223-241
CrossRef219
Jorg Kotzka, Dirk Müller-Wieland. (2004) Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?. Expert Opinion on Therapeutic Targets 8:2, 141-149
CrossRef220
Neil Ruderman, Marc Prentki. (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nature Reviews Drug Discovery 3:4, 340-351
CrossRef221
Stephanie Ann Moran, Nicole Patten, Janice Ryan Young, Elaine Cochran, Nancy Sebring, James Reynolds, Ahalya Premkumar, Alex M Depaoli, Monica C Skarulis, Elif Arioglu Oral, Phillip Gorden. (2004) Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism 53:4, 513-519
CrossRef222
Garg, Abhimanyu, . (2004) Acquired and Inherited Lipodystrophies. New England Journal of Medicine 350:12, 1220-1234
Full Text223
Arati Wagh, Neil J Stone. (2004) Treatment of metabolic syndrome. Expert Review of Cardiovascular Therapy 2:2, 213-228
CrossRef224
Michael McNally, Roslyn B. Mannon, Edward D. Javor, S. John Swanson, Douglas A. Hale, Phillip Gorden, Allan D. Kirk. (2004) Successful Renal Transplantation in a Patient with Congenital Generalized Lipodystrophy: A Case Report. American Journal of Transplantation 4:3, 447-449
CrossRef225
Michal Krsek, Josef V. Silha, Jana Jezkova, Vaclav Hana, Josef Marek, Vladimir Weiss, Jan J. Stepan, Liam J. Murphy. (2004) Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome. Clinical Endocrinology 60:3, 350-357
CrossRef226
James R. Levy, John N. Clore, Wayne Stevens. (2004) Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 39:3, 608-616
CrossRef227
Esra Asilmaz, Paul Cohen, Makoto Miyazaki, Pawel Dobrzyn, Kohjiro Ueki, Gulnorakhon Fayzikhodjaeva, Alexander A. Soukas, C. Ronald Kahn, James M. Ntambi, Nicholas D. Socci, Jeffrey M. Friedman. (2004) Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. Journal of Clinical Investigation 113:3, 414-424
CrossRef228
Graeme Moyle, Jussi Sutinen. (2004) Managing HIV lipoatrophy. The Lancet 363:9407, 412-414
CrossRef229
Ashok Balasubramanyam, Rajagopal V Sekhar, Farook Jahoor, Peter H Jones, Henry J Pownall. (2004) Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of ‘systemic steatosis’. Current Opinion in Lipidology 15:1, 59-67
CrossRef230
Kanako Nishikai, Hiroshi Hirose, Tatsuya Ishii, Matsuhiko Hayashi, Ikuo Saito, Takao Saruta. (2004) Effects of Leptin Receptor Gene 3'-untranslated Region Polymorphism on Metabolic Profiles in Young Japanese Men. Journal of Atherosclerosis and Thrombosis 11:2, 73-78
CrossRef231
Pedro IGLESIAS, Pilar ALVAREZ FIDALGO, Rosa CODOCEO, Juan J. DÍEZ. (2004) Lipoatrophic Diabetes in an Elderly Woman: Clinical Course and Serum Adipocytokine Concentrations. Endocrine Journal 51:3, 279-286
CrossRef232
Kim S Bell-Anderson, Janet M Bryson. (2004) Leptin as a Potential Treatment for Obesity. Treatments in Endocrinology 3:1, 11-18
CrossRef233
Tom A. B. Sanders. (2003) Dietary fat and postprandial lipids. Current Atherosclerosis Reports 5:6, 445-451
CrossRef234
Katharine R. Owen, Mollie Donohoe, Sian Ellard, Andrew T. Hattersley. (2003) Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene. Diabetic Medicine 20:10, 823-827
CrossRef235
Robert A Hegele. (2003) Monogenic forms of insulin resistance: apertures that expose the common metabolic syndrome. Trends in Endocrinology & Metabolism 14:8, 371-377
CrossRef236
Rebecca Mattison, Michael Jensen. (2003) The adipocyte as an endocrine cell. Current Opinion in Endocrinology & Diabetes 10:5, 317-321
CrossRef237
Tara M. Riddle, Carl J. Fichtenbaum, David Y. Hui. (2003) Leptin Replacement Therapy But Not Dietary Polyunsaturated Fatty Acid Alleviates HIV Protease Inhibitor–Induced Dyslipidemia and Lipodystrophy in Mice. JAIDS Journal of Acquired Immune Deficiency Syndromes 33:5, 564-570
CrossRef238
Manel Pladevall, Keoki Williams, Heidi Guyer, Josep Sadurní, Carles Falces, Anna Ribes, Carles Paré, Carlos Brotons, Rafael Gabriel, Manuel Serrano-Ríos, Steven Haffner. (2003) The association between leptin and left ventricular hypertrophy. Journal of Hypertension 21:8, 1467-1473
CrossRef239
Luc F. Van Gaal, Ilse L. Mertens, Pascale J. Abrams. (2003) Health risks of lipodystrophy and abdominal fat accumulation: therapeutic possibilities with leptin and human growth hormone. Growth Hormone & IGF Research 13, S4-S9
CrossRef240
Corinne Vigouroux, Mustapha Maachi, Thu-Huyen Nguyên, Christiane Coussieu, Shahin Gharakhanian, Tohru Funahashi, Yuji Matsuzawa, Iichiro Shimomura, Willy Rozenbaum, Jacqueline Capeau, Jean-Philippe Bastard. (2003) Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 17:10, 1503-1511
CrossRef241
Abhimanyu Garg, Anoop Misra. 2003. Lipodystrophies and Diabetes. .
CrossRef242
Michael Stumvoll. (2003) Thiazolidinediones – some recent developments. Expert Opinion on Investigational Drugs 12:7, 1179-1187
CrossRef243
Jean E. Schaffer. (2003) Lipotoxicity: when tissues overeat. Current Opinion in Lipidology 14:3, 281-287
CrossRef244
Guenther Boden, Peter Cheung, Maria Mozzoli, Susan K Fried. (2003) Effect of thiazolidinediones on glucose and fatty acid metabolism in patients with type 2 diabetes. Metabolism 52:6, 753-759
CrossRef245
O. Moran, M. Phillip. (2003) Leptin: obesity, diabetes and other peripheral effects - a review. Pediatric Diabetes 4:2, 101-109
CrossRef246
Nasser Mikhail. (2003) Insulin resistance in HIV-related lipodystrophy. Current Hypertension Reports 5:2, 117-121
CrossRef247
G. Sonia Nagy, Sotirios Tsiodras, Lizabeth D. Martin, Anchalee Avihingsanon, Alina Gavrila, William C. Hsu, Adolf W. Karchmer, Christos S. Mantzoros. (2003) Human Immunodeficiency Virus Type 1–Related Lipoatrophy and Lipohypertrophy Are Associated with Serum Concentrations of Leptin. Clinical Infectious Diseases 36:6, 795-802
CrossRef248
David Y. Hui. (2003) Effects of HIV protease inhibitor therapy on lipid metabolism. Progress in Lipid Research 42:2, 81-92
CrossRef249
Joseph Proietto, Anne W Thorburn. (2003) The therapeutic potential of leptin. Expert Opinion on Investigational Drugs 12:3, 373-378
CrossRef250
Alexandra Calmy, Bernard Hirschel, Didier Hans, Véronique L Karsegard, Christoph A Meier. (2003) Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. AIDS 17:5, 770-772
CrossRef251
Roger H. Unger. (2003) T
HE PHYSIOLOGY OF CELLULAR LIPOREGULATION 1. Annual Review of Physiology 65:1, 333-347
CrossRef252
Tom A.B. Sanders. (2003) High- versus low-fat diets in human diseases. Current Opinion in Clinical Nutrition and Metabolic Care 6:2, 151-155
CrossRef253
Anoop Misra, Abhimanyu Garg. (2003) Clinical Features and Metabolic Derangements in Acquired Generalized Lipodystrophy. Medicine 82:2, 129-146
CrossRef254
David E. Cummings, Michael W. Schwartz. (2003) Genetics and Pathophysiology of Human Obesity. Annual Review of Medicine 54:1, 453-471
CrossRef255
Yueran Zhao, Rui Sun, Li You, Chunyi Gao, Zhigang Tian. (2003) Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochemical and Biophysical Research Communications 300:2, 247-252
CrossRef256
Dennis C. Mynarcik, Terry Combs, Margaret A. McNurlan, Philipp E. Scherer, Eugene Komaroff, Marie C. Gelato. (2002) Adiponectin and Leptin Levels in HIV-Infected Subjects With Insulin Resistance and Body Fat Redistribution. JAIDS Journal of Acquired Immune Deficiency Syndromes 31:5, 514-520
CrossRef257
Deborah M. Muoio, G. Lynis Dohm. (2002) Peripheral metabolic actions of leptin. Best Practice & Research Clinical Endocrinology & Metabolism 16:4, 653-666
CrossRef258
Johannes B. Prins. (2002) Adipose tissue as an endocrine organ. Best Practice & Research Clinical Endocrinology & Metabolism 16:4, 639-651
CrossRef259
Julia James, Alastair Carruthers, Jean Carruthers. (2002) HIV-Associated Facial Lipoatrophy. Dermatologic Surgery 28:11, 979-986
CrossRef260
I. Sadaf Farooqi, Giuseppe Matarese, Graham M. Lord, Julia M. Keogh, Elizabeth Lawrence, Chizo Agwu, Veronica Sanna, Susan A. Jebb, Francesco Perna, Silvia Fontana, Robert I. Lechler, Alex M. DePaoli, Stephen O’Rahilly. (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. Journal of Clinical Investigation 110:8, 1093-1103
CrossRef261
B. Anne Eberhard, Norman T. Ilowite. (2002) Panniculitis and lipodystrophy. Current Opinion in Rheumatology 14:5, 566-570
CrossRef262
Franck Mauvais-Jarvis, Rohit N. Kulkarni, C. Ronald Kahn. (2002) Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance. Clinical Endocrinology 57:1, 1-9
CrossRef263
(2002) Leptin-Replacement Therapy in Lipodystrophy. New England Journal of Medicine 346:25, 2008-2010
Full Text264
Kitt Falk Petersen, Elif Arioglu Oral, Sylvie Dufour, Douglas Befroy, Charlotte Ariyan, Chunli Yu, Gary W. Cline, Alex M. DePaoli, Simeon I. Taylor, Phillip Gorden, Gerald I. Shulman. (2002) Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. Journal of Clinical Investigation 109:10, 1345-1350
CrossRef265
D.B. Savage, S. O’Rahilly. (2002) Leptin: a novel therapeutic role in lipodystrophy. Journal of Clinical Investigation 109:10, 1285-1286
CrossRef
- Letters
