Association of fat cell size and paracrine growth factors in development of hyperplastic obesity

1998 ◽  
Vol 275 (6) ◽  
pp. R1898-R1908 ◽  
Author(s):  
Brenda G. Marques ◽  
Dorothy B. Hausman ◽  
Roy J. Martin
Keyword(s):  
Adipose Tissue ◽  
Growth Factors ◽  
Conditioned Medium ◽  
Cellular Proliferation ◽  
Cell Number ◽  
Zucker Rats ◽  
Fat Cell ◽  
Obese Rats ◽  
Paracrine Growth Factors ◽  
Obese Zucker Rats

Inguinal, epididymal, and retroperitoneal adipose tissue from lean and obese Zucker rats, 3–15 wk of age, was used to determine the association among adipocyte size distribution, the presence of paracrine growth factors in adipose tissue, and subsequent changes in adipocyte number. For each specific depot and time point, obese rats had a greater percentage of large adipocytes than did lean rats. A positive correlation ( P < 0.02) was found in obese rats between the percentage of inguinal and epididymal adipocytes in the 140- to 180-μm size range and the ability of conditioned medium prepared from these depots to stimulate cellular proliferation in a bioassay system utilizing preadipocytes from inguinal fat pads of normal rats. Proliferative activity of the conditioned medium from all depots in obese rats was positively correlated ( P < 0.01) to subsequent changes in fat cell number. The data presented here for the inguinal and epididymal depot of obese Zucker rats are consistent with the hypothesis that enlarged adipocytes secrete growth factors that induce preadipocyte proliferation.

Effect of swim training on development of obesity in the genetically obese rat

1982 ◽  
Vol 242 (3) ◽  
pp. R204-R211 ◽  
Author(s):  
J. L. Walberg ◽  
P. A. Mole ◽  
J. S. Stern
Keyword(s):  
Body Composition ◽  
Food Restriction ◽  
Plasma Insulin ◽  
Cell Number ◽  
Skeletal Growth ◽  
Zucker Rats ◽  
Fat Cell ◽  
Full Development ◽  
Obese Rats ◽  
Obese Zucker Rats

Seven-week-old female lean and obese Zucker rats were swim trained or kept sedentary for 8 wk. Another group of obese rats was exercised plus food restricted. During exercise training, obese and lean rats ate more but gained less body weight than sedentary controls. Exercise favorably altered body composition, adipose cellularity, and plasma insulin of the obese rat. Exercise plus food restriction more dramatically affected body composition and adipose cellularity but was no more effective in depressing hyperinsulinemia than exercise alone. Following 8 wk of retirement, dorsal fat cell number remained depressed to formerly exercised obese rats whereas adipose cellularity in other depots, body composition, and plasma insulin were similar to control levels. Thus, exercise delayed but did not prevent the full development of obesity in the Zucker rat. Food restriction along with exercise resulted in more permanent effects on adipose cellularity than exercise alone but stunted muscle and skeletal growth.

scholarly journals Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning

1988 ◽  
Vol 254 (2) ◽  
pp. 483-487 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulange ◽  
R Bazin ◽  
X Le Liepvre ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Gapdh Gene ◽  
Gapdh Activity ◽  
Weanling Rats ◽  
Obese Rats ◽  
Specific Increase ◽  
Obese Zucker Rats

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied during the onset of obesity in the genetically obese (fa/fa) rat by determination of GAPDH activity and hybridizable mRNA amounts in adipose tissue and liver from suckling and weanling rats. GADPH activity remained low throughout the suckling period, and a burst of activity occurred after weaning in both lean and obese pups. As early as 7 days of age, adipose tissue from pre-obese rats displayed a significant increase in enzyme activity, whereas no difference could be detected in the liver. In both suckling (16 days of age) and weanling (30 days of age) obese rats a proportionate increase in GAPDH activity and mRNA amounts was observed in adipose tissue, but not in liver. It is concluded that the obese genotype influences GAPDH gene expression at a pretranslational level and in a tissue-specific manner. This phenomenon could partly contribute to the hyperactive fat accretion in the obese rat, since glycolysis is the major metabolic pathway for lipogenic substrates in adipose tissue.

Relationship of adipocyte size to hyperphagia in developing male obese Zucker rats

1992 ◽  
Vol 262 (1) ◽  
pp. R33-R38 ◽  
Author(s):  
J. R. Vasselli ◽  
J. A. Fiene ◽  
C. A. Maggio
Keyword(s):  
Adipose Tissue ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Lipoprotein Lipase Activity ◽  
Adipocyte Size ◽  
High Fat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Relationship Of ◽  
Cumulative Intake

In growing male obese Zucker rats, hyperphagia reaches a maximum or “breakpoint” and declines at an earlier age with high fat than with chow-type diets. A serial adipose tissue biopsy technique was used to correlate changes of retroperitoneal adipocyte size and feeding behavior in 5- to 7-wk-old male lean and obese rats fed laboratory chow or a 35% fat diet until 30 wk of age. Although chow-fed groups had significantly greater cumulative intake, fat-fed groups had significantly greater body weight gain, retroperitoneal depot weight, and adipocyte number. Mean adipocyte size increased continuously in chow-fed groups but decreased over weeks 20-30 in fat-fed groups, reflecting increased adipocyte number. In fat-fed obese rats, hyperphagia reached a breakpoint at 11 wk and disappeared by 13 wk. In chow-fed obese rats, hyperphagia reached a breakpoint at 15-16 wk and disappeared by 19 wk. Biopsy samples revealed that adipocyte size of fat-fed obese rats was already close to maximal at 10 wk (1.12 micrograms lipid), while that of chow-fed obese rats only approached maximal at 20 wk (0.81 microgram lipid). At these time points, lipoprotein lipase activity paralleled adipocyte size. These data indicate that the duration of the growing obese rat's hyperphagia coincides with adipocyte filling and suggest the existence of feeding stimulatory and inhibitory signals from adipose tissue.

Mechanisms of increased lipoprotein lipase in fat cells of obese Zucker rats

1991 ◽  
Vol 261 (5) ◽  
pp. E653-E660 ◽  
Author(s):  
S. K. Fried ◽  
I. J. Turkenkopf ◽  
I. J. Goldberg ◽  
M. H. Doolittle ◽  
T. G. Kirchgessner ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Lipoprotein Lipase ◽  
Bovine Milk ◽  
Zucker Rats ◽  
Fat Cells ◽  
Fat Cell ◽  
Cell Basis ◽  
Rat Adipocytes ◽  
Obese Rats ◽  
Obese Zucker Rats

The mechanisms underlying the increased activity of lipoprotein lipase (LPL) in adipocytes of genetically obese Zucker rats was studied. Relative rates of LPL synthesis (percent of total protein synthesis) determined by biosynthetic labeling and specific immunoprecipitation were similar in isolated fat cells from lean and obese rats, in the absence or presence of insulin. Insulin stimulated LPL synthesis as a result of a general increase in protein synthesis, and this effect was more marked in the obese fat cells. Levels of LPL mRNA, as a percent of total RNA, were also similar in fat cells from lean and obese rats. In contrast, when the data are calculated on a per fat cell basis, rates of LPL synthesis per fat cell are ninefold higher in obese compared with lean cells, accounting for the increase in LPL activity per fat cell. Fat cells from lean and obese rats showed similar rates of binding and degradation of purified bovine milk 125I-labeled LPL per unit fat cell surface area. Thus, on a per cell basis, rates of LPL turnover are increased in enlarged Zucker rat adipocytes, but there is no specific abnormality in the cellular regulation of LPL. Increases in LPL activity in obese rat adipocytes are related to an overall hyperresponsiveness to insulin effects on protein synthesis.

Weight reduction increases adipose but decreases cardiac LPL in reduced-obese Zucker rats

1991 ◽  
Vol 261 (2) ◽  
pp. E246-E251 ◽  
Author(s):  
D. H. Bessesen ◽  
A. D. Robertson ◽  
R. H. Eckel
Keyword(s):  
Adipose Tissue ◽  
Cardiac Muscle ◽  
Weight Reduction ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Coordinate Changes

Lipoprotein lipase (LPL) activity and mRNA levels were measured in cardiac muscle and adipose tissue from lean, obese, and weight-stable reduced-obese Zucker rats, both fasted and 2 h after feeding. Fasting epididymal fat LPL activity was substantially higher in obese rats relative to lean rats [6.9 vs. 0.2 nmol free fatty acid (FFA).10(6) cells-1.min-1; P = 0.0001], and was higher still in reduced-obese rats (15.7 nmol FFA.10(6) cells-1.min-1; P = 0.002). Adipose tissue LPL increased with feeding in all three groups. In marked contrast, fasting cardiac muscle LPL was lower in obese rats relative to lean (28.8 vs. 38.5 nmol FFA.g-1.min-1; P = 0.0064) and was lower still in reduced-obese rats (14.5 nmol FFA.g-1.min-1; P = 0.0001). LPL mRNA levels increased in adipose tissue along with enzyme activity; however, the magnitude of the changes were relatively small, suggesting that the primary regulatory steps are posttranslational. Weight reduction studies were also carried out in Sprague-Dawley rats with similar results. These studies show that sustained weight reduction results in coordinate changes in tissue-specific LPL, favoring delivery of lipoprotein triglyceride fatty acids to adipose tissue relative to cardiac muscle and the restoration of energy stores.

Body composition and adiposity in LH-lesioned and pair-fed obese Zucker rats

1982 ◽  
Vol 242 (6) ◽  
pp. E437-E444
Author(s):  
K. M. Milam ◽  
R. E. Keesey ◽  
J. S. Stern
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Food Restriction ◽  
Cell Number ◽  
Zucker Rats ◽  
Elevated Plasma ◽  
Protein Deposition ◽  
Lean Control ◽  
Obese Rats ◽  
Obese Zucker Rats

It has been reported previously that lateral hypothalamic (LH) lesions alter body composition including reducing adipocyte cellularity in lean and obese Zucker rats. The present experiment was designed to determine whether these alterations in body composition and adipose cell number are secondary to the reduced energy consumption of LH-lesioned rats or to a direct effect of the hypothalamic lesion. Groups of lean and obese Zucker rats, sustaining lesions of the lateral hypothalamus at 10 wk of age, maintained body weight at 72% that of nonlesioned controls until killed at 32 wk. Pair-feeding nonlesioned rats to the intakes of lean and obese LH-lesioned rats produced a reduction in adipocyte number similar to that caused by lesions. However, neither the lean nor obese LH-lesioned rats displayed an increase in cell number when fed a palatable diet that markedly increased carcass lipids. This finding suggests that adipocyte number may be constrained in LH-lesioned rats. These and further observations that 1) lean control rats maintained a higher body weight than the LH-lesioned rats to which they were pair fed and 2) in obese rats, food restriction further reduced protein deposition and elevated plasma insulin relative to comparably fed LH-lesioned obese rats suggest that the LH syndrome is mimicked by simple food restriction.

scholarly journals Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity

2005 ◽  
Vol 289 (5) ◽  
pp. H1807-H1813 ◽  
Author(s):  
Christine Barandier ◽  
Jean-Pierre Montani ◽  
Zhihong Yang
Keyword(s):  
Adipose Tissue ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cell ◽  
Conditioned Medium ◽  
High Fat Diet ◽  
Zucker Rats ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Obese Zucker Rats

Adipocytes and perivascular adipose tissue are emerging as regulators of vascular function. The effects of adipocytes and perivascular adipose tissue on human smooth muscle cell (SMC) proliferation were investigated. Conditioned medium was prepared from cultured premature and differentiated 3T3-L1 adipocytes and from periaortic adipose tissue from young (3 mo) and old (24 mo) Wistar-Kyoto (WKY) rats, lean and obese Zucker rats (3 mo), and WKY rats fed normal chow or a high-fat diet for 3 mo. Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation, which was abolished by charcoal and proteinase K treatment but was resistant to heat, trypsin, or phospholipase B (to hydrolyze lysophosphatidic acid). Further experiments demonstrated that the growth factor(s) are hydrosoluble and present in the fraction of molecular mass >100 kDa. Moreover, conditioned medium from periaortic adipose tissue stimulated SMC proliferation, which was significantly enhanced in aged rats and in rats fed a high-fat diet but not in obese Zucker rats deficient in functional leptin receptors. In conclusion, mature adipocytes release hydrosoluble protein growth factor(s) with a molecular mass >100 kDa for SMCs. Perivascular adipose tissue stimulates SMC proliferation, which is enhanced in aged WKY and in high-fat, diet-induced obesity but not in leptin receptor-deficient obese Zucker rats. These adipocyte-derived growth factor(s) and the effect of perivascular adipose tissue may be involved in vascular disease associated with aging and obesity.

scholarly journals Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats

1991 ◽  
Vol 279 (1) ◽  
pp. 303-308 ◽  
Author(s):  
L Pénicaud ◽  
P Ferré ◽  
F Assimacopoulos-Jeannet ◽  
D Perdereau ◽  
A Leturque ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Zucker Rats ◽  
Lipogenic Enzymes ◽  
Glut 4 ◽  
Obese Rats ◽  
Before And After ◽  
Plasma Insulin Levels ◽  
Obese Zucker Rats

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.

scholarly journals Differential polypeptide expression in adipose tissue of lean and obese Zucker rats. Evidence of specifically repressed peptides in 7-day-old pre-obese rats

1992 ◽  
Vol 284 (3) ◽  
pp. 813-817
Author(s):  
C Laurent-Winter ◽  
I Dugail ◽  
A Quignard-Boulange ◽  
X Le Liepvre ◽  
M Lavau
Keyword(s):  
Adipose Tissue ◽  
Zucker Rats ◽  
Two Dimensional ◽  
Present Evidence ◽  
Two Dimensional Electrophoresis ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Dimensional Electrophoresis ◽  
Obesity Syndrome ◽  
Good Agreement

Using two-dimensional electrophoresis on total extracts of adipose tissue from young lean (Fa/fa) and obese (fa/fa) Zucker rats, we have investigated the existence of early events at the protein level, before obvious obesity. Our results indicate that the two genotypes do not differ at 3 days of age in terms of polypeptide pattern. By 7 days of age, two polypeptides are transiently repressed in the fatty genotype, leading us to suggest their potential involvement in the onset of obesity. However, most of the differences between the lean and obese rats are detected at 30 days of age, characterized by an increase in the accumulation of several peptides in the adipose tissue of obese rats, in good agreement with the multiple biochemical changes previously identified at this stage of the disease. These results present evidence of new peptides that may be of interest in the study of the obesity syndrome.

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

1997 ◽  
pp. 693-700 ◽  
Author(s):  
A Shimaya ◽  
O Noshiro ◽  
R Hirayama ◽  
T Yoneta ◽  
K Niigata ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Transporter ◽  
Zucker Rats ◽  
Epididymal Adipose Tissue ◽  
Maximum Effect ◽  
Insulin Sensitizer ◽  
Peripheral Insulin Resistance ◽  
Obese Rats ◽  
Obese Zucker Rats

Genetically obese Zucker rats exhibit mild hyperglycaemia and hyperinsulinaemia suggesting the existence of peripheral insulin resistance. We have examined the effects of YM268, an analogue of thiazolidinedione, on the content and translocation of a glucose transporter (GLUT4) in epididymal adipose tissue in 11-week-old obese and lean Zucker rats. The administration of YM268 at a dose of 10 mg/kg for 2 weeks ameliorated hyperglycaemia, hyperinsulinaemia, and impaired glucose tolerance after glucose load in obese rats. The GLUT4 content per fat pad in obese rats was reduced to 36% of that in lean littermates. Obese rats treated with YM268 increased GLUT4 concentrations in their fat pads from a basal value of 36% up to 191% of the level in lean rats. Furthermore, in adipocytes prepared from obese rats, an increase in the ratio of GLUT4 in plasma membrane to the total amount of GLUT4 (PM-GLUT4 ratio) induced by the submaximal concentration of insulin (0.3 nmol/l) was significantly attenuated compared with that in lean rats. But the maximum effect of insulin (3 nmol/l) was not attenuated. Meanwhile, YM268 had no significant effect on the attenuated PM-GLUT4 ratio in response to insulin in obese rats. These data suggested that one of the mechanisms by which YM268 improved insulin resistance in obese Zucker rats was to normalize the decreased GLUT4 content in the adipose tissue.

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