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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue lipoprotein lipase (LPL) is a key enzyme responsible for the clearance of circulating triglycerides and has been linked to certain pathologic states such as obesity. In order to investigate whether an animal's endogenous fat-preference is associated with differences in adipose tissue LPL, we measured enzyme activity in epididymal fat from high- and low-fat preferring rats. Utilizing a 24h ad libitum feeding paradigm, four groups of outbred adult male Sprague-Dawley rats were screened separately for their macronutrient preferences. Animals exhibiting high- or low-fat preferences were identified and placed back on standard chow. LPL activity was measured in epididymal fat under chow fed or fasted conditions. Epididymal fat LPL activity was significantly less in the high-fat-preferring animals relative to the low-fat-preferring, in both the standard chow-fed state (p = 0.014) and fasted (p = 0.0007) state. LPL activity in heart ventricle and brown adipose tissue was also measured from the same animals. Activity in heart ventricle and brown adipose tissue was significantly lower in the high-fat-preferring group as compared with the low-fat-preferring only following a 24h fast (p = 0.0012 for heart and p = 0.0085 for brown adipose, high- versus low-fat preferring). The data indicate that differences in tissue LPL activity exist between animals with inherent differences in fat preference. Future comparative studies between the two groups of fat-preferring animals could lead to important clues to the regulation of the LPL.
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PMID:Epididymal fat depot lipoprotein lipase activity is lower in animals with high endogenous fat preferences. 763 Mar 12

The obese (ob) gene has recently been isolated through a positional cloning approach, the mutation of which causes a marked hereditary obesity and diabetes mellitus in mice. In the present study, we isolated rat ob cDNA and examined the tissue distribution of the ob gene expression in rats. We also studied the gene expression in genetically obese Zucker fatty (fa/fa) rats. The rat ob gene product, a 167 amino acid protein with a putative signal sequence, was 96 and 83% homologous to the mouse and human ob proteins, respectively. Northern blot analysis using the rat ob cDNA probe identified a single mRNA species of 4.5 kb in size in the adipose tissue, while no significant amount of ob mRNA was present in other tissues in rats. The ob gene was expressed in the adipose tissue with region specificities. The rank order of the ob mRNA level in the adipose tissue was epididymal, retroperitoneal, and pericardial white adipose tissue > mesenteric and subcutaneous white adipose tissue > or = interscapular brown adipose tissue. The ob gene expression occurred in mature adipocytes rather than in stromalvascular cells isolated from the rat adipose tissue. Expression of the ob gene was markedly augmented in all the adipose tissue examined in Zucker fatty (fa/fa) rats at the stage of established obesity. The present study leads to the better understanding of the physiologic and pathophysiologic roles of the ob gene.
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PMID:Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats. 765 34

Intracellular Ca2+ homeostasis is impaired in tissues from obese humans and rats and insulin loses its regulatory effect on the plasma membrane (Ca2+ + Mg2+)-ATPase in kidney basolateral membranes (BLM) from the genetically obese fa/fa rats. We have demonstrated that loss of insulin regulation of the ATPase may impair insulin biologic effects and may therefore contribute to the insulin resistance in the obese rodents. To test whether the defect is restricted to one species or to one gene of obesity, studies were extended to an additional genetically obese rodent of another species the C57BL/6J ob/ob mice. Twelve-weeks-old obese and control male mice were used and (Ca2+ + Mg2+)-ATPase activity and its regulation by insulin were evaluated in their kidney BLM. The obese mice were heavier (56.4 +/- 2.5 vs 30.5 +/- 1.2 g P < 0.05), were hyperinsulinemic (6.32 +/- 1.87 vs 0.59 +/- 0.13 ng/ml P < 0.05) and had decreased (by 80%) specific binding of insulin to their epididymal fat cells compared with their non-obese littermates controls (ob/+, +/+). Yet, non-fasting plasma glucose levels were similar in the obese and control mice (227.0 +/- 19.3 vs 226.8 +/- 13.7 mg/dl N.S.). Basal activity of the (Ca2+ + Mg2+)-ATPase was similar in membranes from the ob/ob and control mice. However, while insulin (1-40 ng/ml) stimulated the ATPase activity in BLM form controls in a dose dependent manner (15-52%), no effect of insulin on the enzyme was seen in BLM from the obese mice even in the presence of the highest (40 ng/ml) concentration of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different genes for obesity are associated with insulin loss of regulation of the membrane (Ca2+ + Mg2+)-ATPase in the obesity syndrome. Lessons from animal models. 773 47

We explored the possibility that early replacement of low triiodothyronine (T3) may improve the low oxidative metabolism in metabolically important tissues of ob/ob mice. Triiodothyronine doses (2.5 to 25.0 micrograms/100 g body wt) were injected intraperitoneally into ob/ob and non-ob/ob mice daily from 3 wk until 6 wk of age. Untreated ob/ob and non-ob/ob mice were injected with saline (pH 9.1). Food intake was equalized across all groups. At 6 wk of age, the O2 consumption of muscle, white and brown adipose tissues, and hepatocytes was measured. The saline-treated ob/ob mice showed lower muscle weights, higher fat pad and liver weights, and larger fat cell sizes than saline-treated non-ob/ob mice. In ob/ob mice, tissue O2 consumption was the same in muscle, lower in brown and white adipose tissues, but higher in liver compared with values in non-ob/ob mice. Triiodothyronine treatment in ob/ob mice resulted in lower values for body weight, liver weight, hepatocyte number, liver protein, epididymal fat pad weight, and white adipocyte number and size than in saline-treated ob/ob mice. Triiodothyronine treatment increased soleus muscle, liver and brown adipose tissue O2 consumption in non-ob/ob mice. In ob/ob mice, triiodothyronine increased only soleus muscle O2 consumption and required higher doses than in non-ob/ob mice to achieve an effect. These data are consistent with the concept of tissue triiodothyronine resistance in ob/ob mice. Low triiodothyronine levels and tissue resistance to triiodothyronine might be important early defects in this obesity syndrome.
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PMID:Early treatment of obese (ob/ob) mice with triiodothyronine increases oxidative metabolism in muscle but not in brown adipose tissue or liver. 781 68

High fat feeding is associated with impaired insulin action, an obese body composition, and down-regulation of glucose transporter-4 (GLUT4) expression in adipocytes. We recently showed that overexpression of GLUT4 selectively in adipocytes of transgenic mice using the aP2 (fatty acid-binding protein) promoter/enhancer results in enhanced glucose tolerance and adipocyte hyperplasia. Here, we fed these GLUT4-overexpressing transgenic mice a high fat (55%) or a low fat (10%) diet for 13-15 weeks to determine the role of alterations in GLUT4 expression in adipocytes in the development of insulin resistance and obesity, which are characteristic of high fat consumption. In nontransgenic mice, high fat feeding results in 45-50% reduction of GLUT4 levels in white and brown adipose tissue, with a parallel decrease in insulin-stimulated glucose transport. In transgenic mice receiving the low fat diet, GLUT4 is overexpressed 20-fold in white and 4-fold in brown adipose tissue. Glucose transport in epididymal adipocytes is increased 20-fold in the basal state and 6-fold in the insulin-stimulated state. Even after transgenic mice are fed a high fat diet, GLUT4 expression and glucose transport in their adipocytes remains 14- to 30-fold greater than that in nontransgenic mice receiving the same diet. Despite these marked effects at the adipose cell level, glucose tolerance is not improved, probably due to insulin resistance in skeletal muscle and liver, where the transgene is not expressed. During the low fat diet, transgenic mice have 80% more body lipid than nontransgenics. High fat feeding increases body lipid 76% and adipocyte size 65% in nontransgenic mice, but has no effect in transgenic mice. Thus, overexpression of GLUT4 selectively in adipocytes protects against a further increase in adiposity. Furthermore, by using a heterologous promoter, high level overexpression of GLUT4 can be maintained even under metabolic conditions where it is normally down-regulated in adipocytes. This overexpression results in markedly increased glucose transport at the cellular level, but adipose-specific GLUT4 overexpression does not prevent the decrease in glucose tolerance associated with high fat feeding.
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PMID:High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. 786 10

The objective was to assess the effect of a new, highly selective beta 3-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.
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PMID:Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. 791 Apr 36

We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100% higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103% higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79% (3H2O) and 250% (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity.
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PMID:Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats. 800 Mar 47

The purpose of the present study was to characterize the time course of adaptation (i.e., circulating metabolites and hormones, fat pad mass, lipoprotein lipase) to a high-fat diet in obesity-prone (OP) and obesity-resistant (OR) male Wistar rats. Delineation of OP and OR was based on body weight gain (upper tertile for OP; lower tertile for OR) after 1 wk on a high-fat diet (60% of kcal from corn oil). Rats were killed after 1, 2, or 5 wk of the dietary period. Increased body weight and percent body fat in OP rats at 1 wk could not be accounted for by increased retroperitoneal or epididymal fat pad weight. Plasma nonesterified fatty acids and triglycerides, as well as blood concentrations of glucose, lactate, and glycerol, were similar throughout the study. Plasma insulin was significantly greater in OP vs. OR rats and low-fat diet (LFD; 20% of kcal from corn oil) controls at 5 wk only, and blood beta-hydroxybutyrate (mM) was significantly higher in OR compared with OP and LFD rats at 1, 2, and 5 wk. Lipoprotein lipase mRNA and activity were significantly greater in epididymal fat pad and significantly lower in gastrocnemius muscle of OP vs. OR rats at 1 wk. Results suggest that early (i.e., 1 wk) differences in body weight and fat weight between OP and OR rats are not due to fat deposition in retroperitoneal or epididymal fat depots, and tissue-specific changes in LPL (increase in epididymal fat pad and decrease in gastrocnemius muscle) that occur in OP compared with OR rats after 1 wk on a high-fat diet provide a metabolic environment favoring fat storage.
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PMID:Time course of adaptation to a high-fat diet in obesity-resistant and obesity-prone rats. 809 9

The genetically obese Zucker rat is a well-characterized model of early-onset human obesity. The 120 kDa protein was recently found in the liver cytosol of obese Zucker rats at levels higher than that in lean Zucker rats. We isolated this protein using precipitation with ammonium sulfate, DEAE-Sephacel chromatography, and preparative polyacrylamide gel electrophoresis; the product showed a single band on SDS-polyacrylamide gel electrophoresis. Immunoblotting analysis revealed that the 120 kDa protein was predominantly localized in the liver cytosol of obese Zucker rats. The amount of this protein in lean Zucker rats was less than one-fifth of that found in obese Zucker rats. Further, there were only trace amounts of this protein in the lung tissues, and no detectable amount in other tissues, such as kidney, epididymal adipose tissue, brain, spleen, skeletal muscle, or serum, in either strain of rat. These data suggest that the 120 kDa protein contributes to the abnormal lipid metabolism in obese Zucker rats.
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PMID:Isolation and localization of the 120 kDa protein in the liver of genetically obese Zucker rats. 818 33

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.
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PMID:Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. 820 15


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