Original Article
The Effects of Weight Loss on the Activity and Expression of Adipose-Tissue Lipoprotein Lipase in Very Obese Humans
N Engl J Med 1990; 322:1053-1059April 12, 1990
- Abstract
- Abstract
Lipoprotein lipase is an enzyme in adipose tissue that hydrolyzes circulating triglycerides and thereby generates the fatty acids used in the synthesis of triglyceride in fat cells. To determine whether the activity and expression of lipoprotein lipase are affected by weight loss, we studied lipoprotein lipase in the adipose tissue of nine very obese subjects before and after a program of weight reduction.
The subjects' mean (±SEM) initial weight was 136±7.3 kg, and the body-mass index (weight in kilograms divided by the square of the height in meters) ranged from 33.3 to 52.8 (mean, 43.0±2.5). Biopsies of adipose tissue were performed before weight loss and after it, when weight had been stable for three months. The weight reduction was achieved by a very-low-calorie diet (mean weight loss, 42.5±6.8 kg). After weight loss, the level of heparin-releasable lipoprotein lipase activity increased in all patients, from 3.8±1.1 to 7.1 ±1.6 neq of free fatty acid released per minute per 106 cells (P<0.05). In addition, the amount of lipoprotein lipase immunoreactive protein increased from 6.3±1.7 to 24.4±6.9 ng per 106 cells (P<0.05), and there was also an increase in the level of lipoprotein lipase messenger RNA as measured by Northern blotting. There was a strongly positive correlation between the initial body-mass index and the magnitude of the increase in lipoprotein lipase activity (r = 0.80, P<0.01) and immunoreactive protein (r = 0.92, P<0.01).
We conclude that weight loss in very obese subjects leads to the increased activity and expression of lipoprotein lipase, thereby potentially enhancing lipid storage and making further weight loss more difficult. (N Engl J Med 1990;322:1053–9.)
Article Activity
- Article
OBESITY is a complex condition characterized by disordered regulation of the energy balance.1 Although much research has focused on the behavioral, metabolic, and genetic aspects of obesity, the regulation of lipid deposition into adipose tissue is still incompletely understood. Lipoprotein lipase is an enzyme in adipose tissue that may be important for the regulation of body weight in several ways. In the capillaries of fat tissue, lipoprotein lipase hydrolyzes the triglyceride of circulating triglyceride-rich lipoproteins into free fatty acids. These free fatty acids are then taken up by the tissue, reesterified, and stored in the lipid droplets of adipocytes.2 Although human adipose tissue can synthesize free fatty acids from hexoses, free fatty acids for lipid storage are preferentially obtained from lipoprotein lipase—mediated hydrolysis of chylomicrons and very-low-density lipoproteins.3 In addition, lipoprotein lipase has been proposed to be an initiator of a peripheral signal from adipose tissue to the central nervous system in obese rodents that results in the stimulation of food consumption.4 Hence, lipoprotein lipase has been referred to as the "gatekeeper of the adipocyte"4 because of these potentially important adipose-storage functions.
If indeed lipoprotein lipase represents such a gatekeeper, then one would expect it to be regulated by alterations in body weight that result from changes in behavior. A number of studies have examined the catalytic activity of lipoprotein lipase in adipose tissue in obesity. When adipose lipoprotein lipase has been measured in obese subjects after they have fasted, an increase in lipoprotein lipase activity per adipocyte has been demonstrated consistently.5 6 7 8 9 10 11 However, conflicting data have been obtained on the effects of weight loss on lipoprotein lipase activity. Some studies have shown an increase in lipoprotein lipase activity in fasting subjects who have lost weight,12 , 13 whereas others have found no change or a decrease in activity.8 , 14 15 16 17
Recent studies have reported techniques that permit the direct measurement of the lipoprotein lipase protein and messenger RNA (mRNA) in adipose tissue.18 19 20 Using these techniques, we have examined the mechanism of the change in adipose lipoprotein lipase activity after weight loss and weight stabilization in nine obese subjects.
Methods
Subjects
Nine obese subjects were recruited from the weight-control program at Cedars—Sinai Medical Center and gave informed consent to the procedure. None of the subjects had diabetes or any other serious medical problems, and none were taking any medications that would affect lipid metabolism. A biopsy of adipose tissue was performed in each subject before and after weight loss. Before the first adipose-tissue biopsy, the subjects reported that their weight had been stable for at least two months. On the day before the fat biopsy, each subject followed a standard isocaloric diet consisting of 50 percent carbohydrate, 20 percent protein, and 30 percent fat. The subjects then fasted for 12 hours, and a subcutaneous fat biopsy was performed, as described previously,21 in the lower abdominal wall, with the removal of 3 to 15 g of fat. A portion of the excised tissue was placed in iced phosphate-buffered saline and processed immediately for assays of lipoprotein lipase activity and immunoreactive protein. A second portion of the adipose tissue was immediately frozen in liquid nitrogen and stored at −70°C for subsequent isolation of RNA. The subjects then undertook a program of weight reduction consisting of a very-low-calorie diet (Health Management Resources, Freeport, N.Y.), together with behavior modification and nutritional education. After each subject had lost weight, resumed a normal diet, and maintained the weight loss for at least three months, a second fat biopsy was performed. Subjects then followed a standard isocaloric diet for one day and, after a 12-hour fast, underwent an adipose-tissue biopsy on the side of the abdomen opposite the first biopsy site. The tissue was processed in the same manner as described above. This protocol was approved by the Cedars—Sinai Medical Center institutional review board.
Catalytic Activity of Lipoprotein Lipase
Lipoprotein lipase activity was separated into two fractions, as described previously21: activity released by heparin and activity extracted from the tissue after the heparin-induced release. To prepare the heparin-releasable fraction, adipose tissue was minced and incubated with 13 μg of heparin per milliliter (Fisher, Pittsburgh) in phosphate-buffered saline for 45 minutes at 37°C. An aliquot of incubation medium was then assayed for lipoprotein lipase activity as described below. The heparin-treated tissue was then washed once with phosphate-buffered saline, and the extractable fraction was prepared by homogenizing the tissue in buffer containing deoxycholate and heparin, as described previously.19 , 22 The sample was centrifuged, and the aqueous layer was collected and assayed in triplicate for lipoprotein lipase activity.
The assay of lipoprotein lipase activity was performed as described previously.23 We used a substrate containing [14C] triolein emulsified with lecithin and normal human serum as a source of apolipoprotein C-II. The samples were incubated with the substrate solution for 45 minutes at 37°C, and 14C-labeled free fatty acids were separated according to the method of Beifrage and Vaughn.24 Lipoprotein lipase activity was expressed as nanoequivalents of free fatty acid released per minute per 106 cells, and the numbers of cells were determined according to the method of Di Girolamo et al.25
Lipoprotein Lipase Immunoreactive Protein
To determine the mass of lipoprotein lipase immunoreactive protein, tissue samples were prepared as described above for the assay of lipoprotein lipase activity, except for the addition of protease inhibitors.19 The enzyme-linked immunosorbent assay (ELISA) for measuring the mass of lipoprotein lipase immunoreactive protein has been described previously; the data were expressed as nanograms of immunoreactive lipoprotein lipase per 106 cells.19 In brief, a microtiter plate was coated with affinity-purified chicken and—lipoprotein lipase antibody, and samples and bovine lipoprotein lipase standards were applied in a buffer containing 1 M sodium chloride, 0.1 percent Triton X-100, 0.1 percent albumin, protease inhibitors, and 25 mM TRIS hydrochloric acid (pH 7.4). Biotinylated anti—lipoprotein lipase antibody was then added, followed by streptavidin-horseradish peroxidase (Bethesda Research Laboratories, Bethesda, Md.). The color reaction was quantitated on an ELISA plate reader at 490 nm. Samples obtained before and after the subjects lost weight were assayed in duplicate on the same ELISA plate to minimize interassay variation.
Western Blotting
As described previously,21 samples of adipose tissue were homogenized with the deoxycholate—heparin buffer described above for the extractable fraction, except that protease inhibitors (but not albumin) were present. After electrophoresis was performed under denaturing conditions on a 12 percent sodium dodecyl sulfate–polyacrylamide gel, the resolved proteins were transferred electrophoretically to a nitrocellulose membrane, which was incubated with anti-lipoprotein lipase antiserum, followed by rabbit antichicken antiserum (Sigma, St. Louis) and [125I]protein A (Amersham, Arlington Heights, Ill.). The lipoprotein lipase bands were then visualized by autoradiography.
Extraction of RNA and Northern Blot and Slot-Blot Analysis
The isolation of RNA from adipose tissue was performed according to the guanidinium thiocyanate—phenol—chloroform method of Chomczynski and Sacchi,26 and RNA was quantitated spectrophotometrically. As described previously, the extracted RNA samples were either subjected to electrophoresis on a 2.2 M formaldehyde—1 percent agarose gel and transferred to a nylon membrane (Hybond-N; Amersham) for Northern blot analysis or blotted directly onto a nylon membrane with a slot-blot manifold apparatus (Schleicher and Schuell, Keene, N.H.) for slot-blot analysis. Northern and slot blots were loaded with equal quantities of total RNA. Loading gels according to the quantity of RNA yielded the same results as loading them according to the number of adipocyte cells or DNA content27 of the original sample of adipose tissue. The blotted membranes were hybridized to 32P-labeled complementary DNA (cDNA) probes28 coding for human lipoprotein lipase20 and gamma-actin.29 After hybridization and washing of the membranes as described elsewhere,21 the images were quantitated by autoradiography and densitometry.
Statistical Analysis
Data were expressed as means ±SEM, and the differences between groups were analyzed with the paired two-tailed t-test. The data in Figure 3Figure 3
Relation between Increase in Lipoprotein Lipase and the Initial Degree of Adiposity. were analyzed by linear regression analysis.Results
The characteristics of the obese subjects recruited for this study are shown in Table 1Table 1
Characteristics of the Study Subjects.. The mean initial body-mass index (weight in kilograms divided by the square of the height in meters) was 43.0, indicating that these patients were quite obese. In addition, they lost a considerable amount of weight and maintained this weight loss for at least three months. The mean weight loss was 42.5 kg (30.4 percent of initial weight), and the weight loss ranged from 16.0 to 65.7 kg (12.5 to 46.6 percent of initial weight). Despite the magnitude of obesity in these subjects, they were in good overall health. The individual values for serum lipid and fasting glucose levels before weight loss are shown in Table 1. Weight loss resulted in an overall improvement in serum lipid levels. The mean (±SEM) fasting lipid levels after weight loss were 0.81 ±0.11 mmol per liter for triglyceride, 4.6±0.31 mmol per liter for cholesterol, and 1.3±0.13 mmol per liter for high-density lipoprotein.Lipoprotein lipase activity and the mass of immunoreactive protein were measured in adipose-tissue samples obtained from subjects before and after weight reduction. Weight loss resulted in an increase in the lipoprotein lipase activity that could be induced by heparin in all the subjects (Table 2Table 2
Effect of Weight Loss on Lipoprotein Lipase Activity and Mass in the Nine Obese Subjects.). Before weight loss, such activity was 3.8±1.1 neq of free fatty acid released per minute per 106 cells and increased to 7.1 ±1.6 neq of free fatty acid released per minute per 106 cells after the weight loss. The level of heparin-releasable lipoprotein lipase immunoreactive protein also increased with weight loss, from 6.3±1.7 to 24.4±6.9 ng per 106 cells (Table 2), suggesting that the increase in lipoprotein lipase activity was due to an increase in lipoprotein lipase protein. As noted previously, 19 , 21 extractable lipoprotein lipase activity represented a minor fraction of the total lipoprotein lipase activity in adipose tissue, yet extractable immunoreactive protein represented a large proportion of the total lipoprotein lipase immunoreactive protein in adipose tissue. However, neither extractable activity nor mass was significantly affected by weight loss. Although the increase in the mass of heparin-releasable lipoprotein lipase immunoreactive protein was somewhat larger than the increase in heparin-releasable activity, there was no significant difference in the specific activity of lipoprotein lipase as a result of weight loss.Previous studies have suggested that lipoprotein lipase activity may be regulated through glycosylation or other post-translational events.21 , 30 , 31 To determine whether weight loss resulted in any detectable changes in the activity of lipoprotein lipase protein, Western blotting was performed on extracts of adipose tissue. Extracts of adipose tissue obtained before and after weight loss from two representative subjects underwent sodium dodecyl sulfate–polyacrylamide gel electrophoresis, were transferred to nitrocellulose gel, and were blotted with the anti—lipoprotein lipase antiserum (see Methods). The gels were loaded with adipose homogenate corresponding to equal numbers of cells. The results are shown in Figure 1Figure 1
Western Blot of Lipoprotein Lipase (LPL) Protein.; below each lane is the corresponding data for lipoprotein lipase activity and the mass of immunoreactive protein. The intensity of the 55-kd band corresponding to the lipoprotein lipase protein was increased in the samples obtained after the subjects lost weight, but the molecular weight was unchanged. Thus, the autoradiographic image on the Western blot corresponds to the data on immunoreactive mass obtained by ELISA, and no other forms of lipoprotein lipase were detected with the use of Western blotting.To examine further the cellular mechanism underlying the increase in lipoprotein lipase activity with weight loss, RNA was extracted and the levels of mRNA in lipoprotein lipase were quantitated. Figure 2Figure 2
Effect of Weight Loss on the Levels of Lipoprotein Lipase (LPL) mRNA. shows a Northern blot of adipose tissue from two subjects before and after they lost weight. When the blot was hybridized with the Radio-labeled human cDNA probe, the intensity of the 3.4-kb (kilobase) and 3.6-kb lipoprotein lipase transcripts of the samples obtained after weight loss was significantly increased as compared with that of the samples obtained before weight loss (Fig. 2). The blot was subsequently hybridized with the Radio-labeled cDNA probe for gamma-actin. A small increase in the level of gamma-actin mRNA was noted, despite the loading of equal quantities of total RNA in each lane. Therefore, each lane was analyzed with use of densitometry, and the ratios of lipoprotein lipase to actin in samples obtained before and after weight loss were compared after the ratio in samples obtained before weight loss had been arbitrarily assigned a value of 1.0. As indicated below each lane in Figure 2, there was a 2.8-fold and a 1.9-fold increase in the ratio of lipoprotein lipase to actin in these two subjects after weight loss. When the Northern and slot blots of all the subjects were examined with use of densitometry, the ratio in the samples obtained after weight loss was twice that in the samples obtained before weight loss.Before weight loss, there was a wide variation in body-mass index in these nine subjects — from 33.3 to 52.8. To examine the relation between the degree of obesity and the response of lipoprotein lipase to weight loss, the individual increases in heparin-releasable lipoprotein lipase activity and the heparin-releasable mass of immunoreactive protein were plotted against each subject's initial body-mass index. As shown in Figure 3, there was a significant correlation between the degree of adiposity, as assessed by the body-mass index, and the increase in heparin-releasable lipoprotein lipase activity (Fig. 3A) and mass of immunoreactive protein (Fig. 3B). Although the subjects who were the most obese tended to lose the most weight, there was no statistically significant relation between the amount of weight lost, expressed either in kilograms or as a percentage of initial weight, and the increase in lipoprotein lipase activity. Thus, the increase in lipoprotein lipase activity was observed in all these subjects, but it was more pronounced in those who were very obese.
Discussion
A number of studies have measured lipoprotein lipase activity in obese subjects at various times before, during, and after a period of hypocaloric diet and weight loss. All studies demonstrated increased lipoprotein lipase activity in obese subjects before dieting5 6 7 8 9 10 11 and a reduction during or soon after the start of the hypocaloric diet.5 , 10 , 15 16 17 , 32 However, different results were obtained after the reinstitution of an isocaloric diet. When adipose-tissue biopsies were performed after the subjects' weight had been stable for two to six weeks, the activity of adipose lipoprotein lipase was decreased in some studies,14 , 15 , 17 and unchanged8 or increased13 in others. Other studies examined lipoprotein lipase activity in adipose tissue after the subjects' weight had been stable for three and six months and found no change16 or a decrease in activity,17 or an exaggerated increase in response to a meal or a glucose-insulin infusion.16 , 17
In the present study, all subjects were studied while they were obese, after their weight had been stable for three months, and after they had followed an isocaloric diet for one day. Fasting lipoprotein lipase activity was increased in all subjects after they lost weight and had maintained the weight loss for three months. In addition, the increase in lipoprotein lipase activity was accompanied by an increase in the mass of lipoprotein lipase immunoreactive protein and in the level of lipoprotein lipase mRNA. Although there was an increase in the activity and expression of lipoprotein lipase with weight loss in all subjects studied, the magnitude of this increase varied. We observed a significant correlation between the initial degree of obesity, using the body-mass index as an index of obesity, and the increase in lipoprotein lipase activity with weight loss.
One possible explanation for the differences between this and previous studies is the differences in the subjects and study design. Our subjects were more obese than those in most other studies. The correlation between the initial body-mass index and the increase in the activity and expression of lipoprotein lipase that we observed suggests that persons with mild to moderate obesity (body-mass index, <35) will have minimal changes in lipoprotein lipase activity after weight loss. In two of the studies that showed no increase in lipoprotein lipase activity with weight loss,16 , 17 the mean initial weight was 85 to 90 kg. In addition, the only other study that demonstrated an increase in lipoprotein lipase activity after weight loss13 included subjects who were almost as obese as those in the present study (mean initial body weight, 121 kg vs. 136 kg in the present study). Another difference between this study and others is the amount of weight the subjects lost before their weight stabilized. Although the subjects who were the most obese tended to lose more weight, there was no consistent correlation between the amount of weight lost and the increase in lipoprotein lipase activity. However, all the subjects lost at least 12 percent of their initial body weight, and the average weight lost was 30 percent of the initial weight. An earlier study suggested that there was a threshold of weight lost that had to be reached before an increase in lipoprotein lipase activity could be seen.33 In other studies involving weight loss and lipoprotein lipase activity, the amount of weight lost ranged from a minimum of 5 percent17 to a maximum of 17 percent14 of the initial body weight.
In a previous study, we demonstrated that the increase in fasting lipoprotein lipase activity in obese subjects was not accompanied by an increase in the mass of lipoprotein lipase immunoreactive protein21 and therefore was probably due to post-translational activation of the lipoprotein lipase protein. The data in the present study demonstrate that the further increase in lipoprotein lipase activity after weight loss occurred through a different cellular mechanism — an increase in the levels of lipoprotein lipase mRNA —suggesting the regulation of transcription or stabilization of mRNA. Because the mechanisms of lipoprotein lipase regulation after food consumption and after weight loss differ, it is likely that lipoprotein lipase is responding to different hormonal influences. After eating and in obese subjects before weight loss, hyperinsulinemia may be the predominant influence, leading to post-translational regulation of lipoprotein lipase activity. With weight loss, patients become more sensitive to insulin in parallel with a decrease in the plasma insulin level.34 If insulin were the only regulatory influence on lipoprotein lipase activity, one might predict that weight loss would not change lipoprotein lipase activity. Thus, the increase in the levels of lipoprotein lipase mRNA with weight loss suggests that lipoprotein lipase is responding to either a different hormonal mediator or some other form of regulation.
Taken together these data suggest several hypotheses regarding the pathogenesis of obesity. The increase in fasting lipoprotein lipase activity in obese subjects resembles mechanistically the increase in lipoprotein lipase activity with feeding: both increases involve a post-translational activation of the lipoprotein lipase protein. Therefore, long-term overeating may induce, in essence, a perpetual state of activation of the lipoprotein lipase protein. In persons who are mildly to moderately obese, caloric intake may be the primary factor controlling the activity of lipoprotein lipase in adipose tissue, in such a way that weight loss and weight stabilization result in no change or a decrease in lipoprotein lipase activity due to the reduced caloric intake. On the other hand, persons who are massively obese overeat but also may have abnormal regulation of lipoprotein lipase, perhaps as a result of genetic factors. Weight loss in these persons would lead to an increase in the expression of the lipoprotein lipase gene, as suggested by the data in the present study. The accumulation of lipids in adipocytes would then be facilitated, and weight gain would be more likely to occur.
A substantial weight gain requires some degree of excess caloric intake, and persons who have lost a great deal of weight often struggle with the urge to overeat. Although much of this tendency is undoubtedly due to behavioral influences, Greenwood4 has speculated that it may be due to the increased release of a putative adipose-tissue messenger that acts on the central nervous system. Such a messenger would maintain the size of adipocytes by signaling the brain to increase caloric intake in response to a perceived hypocaloric state, such as weight loss in obese persons. The increase in lipoprotein lipase activity with weight loss suggests that lipoprotein lipase may be responsible for generating such a message in susceptible subjects and thus may be a key metabolic regulator of adipose mass. Under isocaloric conditions, levels of lipoprotein lipase mRNA may remain constant with feeding and short-term fasting, and this level of expression of lipoprotein lipase would then become an adipocyte set point, controlling the degree of lipid accumulation. Weight loss and the shrinkage of adipocytes in susceptible persons may then perturb this set point and result in an increased expression of lipoprotein lipase. Although lipoprotein lipase may not be the sole determinant of the accumulation of lipids in adipocytes in obese humans, the increase in the activity and expression of lipoprotein lipase may facilitate the storage of fat and perhaps lead to increased eating as well.
Supported by a Career Development Award from the Juvenile Diabetes Foundation, a grant (DK-39176) from the National Institutes of Health, and a fellowship grant from the American Diabetes Association, California Affiliate.
We are indebted to Dr. Lawrence Stiffler of Health Management Resources for supplying the dietary supplement for the study subjects, to Linda Purdy and Sheryl Weber for assistance with the recruitment of subjects, to Dr. John Goers for supplying the anti—lipoprotein lipase antibodies, to Drs. Todd Kirchgessner and Michael Schotz for supplying the lipoprotein lipase cDNA, and to Mildred Wikkeling for assistance in the preparation of the manuscript.
Source Information
From the Department of Medicine, the Division of Endocrinology, Cedars—Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, where reprint requests should be addressed to Dr. Kern at the Division of Endocrinology, Becker 131.
- References
References
1
Bray
Web of Science | Medline2
Eckel
Full Text | Web of Science | Medline3
Idem. Adipose tissue lipoprotein lipase. In: Borensztajn J, ed. Lipoprotein lipase. Chicago: Evener Publishers, 1987:79–132.
4
Greenwood
Web of Science | Medline5
Guy-Grand
CrossRef | Web of Science | Medline6
Pykalisto
CrossRef | Web of Science | Medline7
Taskinen
CrossRef | Web of Science | Medline8
Sorbis
CrossRef | Web of Science | Medline9
Amer
Web of Science | Medline10
Bosello
Web of Science | Medline11
Sadur
CrossRef | Web of Science | Medline12
Schwartz
CrossRef | Web of Science | Medline13
Schwartz
CrossRef | Web of Science | Medline14
Reitman
CrossRef | Web of Science | Medline15
Rebuffe-Scrive
Web of Science | Medline16
Eckel
CrossRef | Web of Science | Medline17
Taskinen
CrossRef | Web of Science | Medline18
Goers
CrossRef | Web of Science | Medline19
Kern
CrossRef | Web of Science | Medline20
Wion
CrossRef | Web of Science | Medline21
Ong
CrossRef | Web of Science | Medline22
Iverius P-H, Östlund-Lindqvist A-M. Preparation, characterization, and measurement of lipoprotein lipase. In: Albers JJ, Segrest JP, eds. Plasma lipoproteins, part B: characterization, cell biology, and metabolism. Vol. 129 of Methods in enzymology. New York: Academic Press, 1986:691–704.
23
Kern
CrossRef | Web of Science | Medline24
Beifrage
Web of Science | Medline25
Di Girolamo
Web of Science | Medline26
Chomczynski
CrossRef | Web of Science | Medline27
Labarca
CrossRef | Web of Science | Medline28
Feinberg
CrossRef | Web of Science | Medline29
Gunning
Web of Science | Medline30
Ong
Web of Science | Medline31
Semb
Web of Science | Medline32
Taskinen
CrossRef | Web of Science | Medline33
Schwartz
Web of Science | Medline34
Glass
Web of Science | Medline
- Citing Articles (32)
Citing Articles
1
Benoit Drolet, Chantale Simard, Paul Poirier. (2007) Impact of Weight-Loss Medications on the Cardiovascular System. American Journal of Cardiovascular Drugs 7:4, 273-288
CrossRef2
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
CrossRef3
Seiichiro Kano, Masako Doi. (2006) NO-1886 (ibrolipim), a lipoprotein lipase–promoting agent, accelerates the expression of UCP3 messenger RNA and ameliorates obesity in ovariectomized rats. Metabolism 55:2, 151-158
CrossRef4
Masataka Kusunoki, Kazuhiko Tsutsumi, Koshi Iwata, Weidong Yin, Takao Nakamura, Hitoshi Ogawa, Tomoko Nomura, Koya Mizutani, Arao Futenma, Keiko Utsumi, Tetsuro Miyata. (2005) NO-1886 (ibrolipim), a lipoprotein lipase activator, increases the expression of uncoupling protein 3 in skeletal muscle and suppresses fat accumulation in high-fat diet–induced obesity in rats. Metabolism 54:12, 1587-1592
CrossRef5
Dean Ornish. (2004) Was Dr Atkins right?. Journal of the American Dietetic Association 104:4, 537-542
CrossRef6
May Faraj, Hui Ling Lu, Katherine Cianflone. (2004) Diabetes, lipids, and adipocyte secretagogues. Biochemistry and Cell Biology 82:1, 170-190
CrossRef7
Joyce A. Corsica, Michael G. Perri. 2003. Obesity. .
CrossRef8
Lalita Khaodhiar, George L. Blackburn. (2002) Obesity treatment: factors involved in weight-loss maintenance and regain. Current Opinion in Endocrinology & Diabetes 9:5, 369-374
CrossRef9
T. Ruge, A. Svensson, J. W. Eriksson, T. Olivecrona, G. Olivecrona. (2001) Food deprivation increases post-heparin lipoprotein lipase activity in humans. European Journal of Clinical Investigation 31:12, 1040-1047
CrossRef10
Tatsuhiro Matsuo, Yoshitake Baba, Mineo Hashiguchi, Kei Takeshita, Ken Izumori, Hiroo Suzuki. (2001) Dietary D-psicose, a C-3 epimer of D-fructose, suppresses the activity of hepatic lipogenic enzymes in rats. Asia Pacific Journal of Clinical Nutrition 10:3, 233-237
CrossRef11
Zafra Cooper, Christopher G Fairburn. (2001) A new cognitive behavioural approach to the treatment of obesity. Behaviour Research and Therapy 39:5, 499-511
CrossRef12
Brian J. Nickoloff. (2001) Creation of psoriatic plaques: the ultimate tumor suppressor pathway.. A new model for an ancient T-cell-mediated skin disease. Viewpoint. Journal of Cutaneous Pathology 28:2, 57-64
CrossRef13
R James Stubbs, Leona O’Reilly. 1999. Carbohydrate and Fat Metabolism, Appetite, and Feeding Behavior in Humans. .
CrossRef14
(1999) The effects of high-fat diet feeding over generations on body fat accumulation associated with lipoprotein lipase and leptin in rat adipose tissues. Asia Pacific Journal of Clinical Nutrition 8:1, 46-52
CrossRef15
Michael G. Perri. (1998) The Maintenance of Treatment Effects in the Long-Term Management of Obesity. Clinical Psychology: Science and Practice 5:4, 526-543
CrossRef16
Junji Kobayashi, Jun Tashiro, Shunichi Murano, Nobuhiro Morisaki, Yasushi Saito. (1998) Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation. Clinical Endocrinology 48:4, 515-520
CrossRef17
Masayuki Ohara, Kazuhiko Tsutsumi, Nakaaki Ohsawa. (1998) Suppression of carcass weight loss in cachexia in rats bearing leydig cell tumor by the novel compound NO-1886, a lipoprotein lipase activator. Metabolism 47:1, 101-105
CrossRef18
E. ŠEBÖKOVÁ, I. KLIMEŠ. (1997) Molecular and Cellular Determinants of Triglyceride Availability. Annals of the New York Academy of Sciences 827:1 Lipids and Sy, 200-214
CrossRef19
Zdzislaw Kochan, Joanna Karbowska, Julian Świerczyński. (1997) Unusual increase of lipogenesis in rat white adipose tissue after multiple cycles of starvation-refeeding. Metabolism 46:1, 10-17
CrossRef20
G. Terence Wilson. (1996) Acceptance and change in the treatment of eating disorders and obesity. Behavior Therapy 27:3, 417-439
CrossRef21
Claude Bouchard. (1996) Can Obesity Be Prevented?. Nutrition Reviews 54:4, S125-S130
CrossRef22
M. Maffei, J. Halaas, E. Ravussin, R.E. Pratley, G.H. Lee, Y. Zhang, H. Fei, S. Kim, R. Lallone, S. Ranganathan, P.A. Kern, J.M. Friedman. (1995) Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1:11, 1155-1161
CrossRef23
R. H. ECKEL, T. J. YOST, D. R. JENSEN. (1995) Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase. European Journal of Clinical Investigation 25:6, 396-402
CrossRef24
Karen M. Carrier, Mary A. Steinhardt, Sally Bowman. (1994) Rethinking Traditional Weight Management Programs: A 3-Year Follow-Up Evaluation of a New Approach. The Journal of Psychology 128:5, 517-535
CrossRef25
John P. Foreyt, G. Ken Goodrick. (1994) Attributes of successful approaches to weight loss and control. Applied and Preventive Psychology 3:4, 209-215
CrossRef26
Leslie I. Katzel, M.Janette Busby-Whitehead, Ellen M. Rogus, Ronald M. Krauss, Andrew P. Goldberg. (1994) Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia. Metabolism 43:2, 190-198
CrossRef27
G.Terence Wilson. (1994) Behavioral treatment of obesity: thirty years and counting. Advances in Behaviour Research and Therapy 16:1, 31-75
CrossRef28
J.C. Stinson, D. Owens, P. Collins, A. Johnson, G.H. Tomkin. (1993) Hyperinsulinaemia is Associated with Stimulation of Cholesterol Synthesis in Both Type 1 and Type 2 Diabetes. Diabetic Medicine 10:5, 412-419
CrossRef29
Jorge A. Vazquez, Siamak A. Adibi. (1992) Protein sparing during treatment of obesity: Ketogenic versus nonketogenic very low calorie diet. Metabolism 41:4, 406-414
CrossRef30
S.W. Coppack, R.D. Evans, R.M. Fisher, K.N. Frayn, G.F. Gibbons, S.M. Humphreys, M.L. Kirk, J.L. Potts, T.D.R. Hockaday. (1992) Adipose tissue metabolism in obesity: Lipase action in vivo before and after a mixed meal. Metabolism 41:3, 264-272
CrossRef31
Kurt Derfler, Michael Hayde, Gottfried Heinz, Michael M Hirschl, Günther Steger, Anna-Christine Hauser, Peter Balcke, Kurt Widhalm. (1991) Decreased postheparin lipolytic activity in renal transplant recipients with cyclosporin A. Kidney International 40:4, 720-727
CrossRef32
M. Katahn, Mark R. Mcminn. (1990) Obesity A Biobehavioral Point of View. Annals of the New York Academy of Sciences 602:1 Psychology, 189-204
CrossRef
