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

We analyzed retrospectively data from 148 chow-fed male Wistar rats killed between the age of 6 wk and 2 yr while varying in body weight from 136 to 917 g. The purpose of this study was to clarify the relationship of body weight and body lipid content with the composition and cellularity of the epididymal and retroperitoneal fat depots. A positive linear association was found between body weight and body water or fat-free dry residue, whereas total body lipid exhibited a curvilinear relationship with body weight. The weight of the epididymal pads was linearly related to body weight but not to body lipid. In contrast, retroperitoneal pad weight was exponentially related to body weight and paralleled total body lipid. A strong linear correlation was found between total body lipid and weight (r = 0.959) or depot lipid content (r = 0.967) of the retroperitoneal fat pads. In this rat model of aging and spontaneous obesity, significant regional differences exist in adipose depot composition and cellularity. A practical outcome of this study is a simple and accurate prediction of body lipid content from the gravimetric determination of the retroperitoneal fat depots.
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PMID:Model of spontaneous obesity in aging male Wistar rats. 226 Jul 22

To study effects of isoprothiolane and phytosterol on dietary fat necrosis, 3 groups of rats were fed hardened-tallow (HT) diet. Two groups of rats received either isoprothiolane (50 mg/kg) or phytosterol (20 mg/kg) orally once a day consecutively for 10 weeks. One group of rats received standard diet (CE-2) as a control. Fat necrotic lesions were observed in epididymal and perirenal adipose tissues from all rats in the 3 groups fed HT diet. Rats with fat necrosis were characterized by visceral type obesity and saturation in fatty acid composition of triglyceride in adipose tissue. The highest glucose conversion to total lipids was seen in adipocytes from the rats given phytosterol. There was no lipolytic response to epinephrine stimulation (1-100 microM) in adipocytes from the rats given only HT diet, while similar response of adipocytes from the 2 groups treated with either drug to those from the rats fed standard diet was observed. The levels of total saturated fatty acids of phospholipid in adipose tissue from the rats given either drug were lower than that of the rats given only HT diet. These data suggest that either drug alters fatty acid composition of phospholipid in fat cell membrane and enhances lipolysis of the cells.
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PMID:Effects of isoprothiolane and phytosterol on lipogenesis and lipolysis in adipocytes from rats of dietary fat necrosis. 228 26

Lipogenic response to feeding was measured in vivo in liver, epididymal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), during the development of obesity in gold-thioglucose (GTG)-injected mice. The fatty acid synthesis after a meal was higher in all tissues of GTG-treated mice on a total-tissue basis, but the magnitude of this increase varied, depending on the tissue and the time after the initiation of obesity. Lipogenesis in BAT from GTG mice was double that of control mice for the first 2 weeks, but subsequently decreased to near control values. In WAT, lipogenesis after feeding was highest 2-4 weeks after GTG injection, and in liver, lipid synthesis in fed obese mice was greatest at 7-12 weeks after the induction of obesity. The post-prandial insulin concentration was increased after 2 weeks of obesity, and serum glucose concentration was higher in fed obese mice after 4 weeks. These results indicate that increased lipogenesis in GTG-injected mice may be due to an increase in insulin concentration after feeding and that insulin resistance (assessed by lipogenic response to insulin release) is apparent in BAT before WAT and liver.
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PMID:Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse. 249 13

The genetic obesity of the fa/fa rat is due to or accompanied by perturbances in the autonomic nervous control of different target tissues (e.g. endocrine pancreas, brown adipose tissue). These disorders are likely to be secondary to central dysregulation(s), which could lie somewhere within or in relationship with the hypothalamus. In view of the reported effects of CRF in stimulating sympathetic nerve-mediated mechanisms, while inhibiting vagus nerve-mediated ones, ovine CRF (oCRF) was administered for 7 days into the cerebral ventricles of fa/fa rats at a dose (5 micrograms/day) that did not affect the pituitary-adrenal axis. oCRF treatment stopped the excessive weight gain of the obese animals; oCRF-treated animals gained only 1 g over 6 days, while the vehicle-treated ones gained 29 g (P = 0.044). The oCRF effect was unrelated to changes in food intake, as the two groups were pair-fed. oCRF-treated obese rats were characterized by a decrease in basal hyperinsulinemia, increases in brown adipose tissue weight and activity, and decreases in hepatic glycogen content and epididymal fat pad weight. It is suggested that intracerebroventricular oCRF administration to obese fa/fa rats prevents the 10-15% increase in body weight observed in vehicle-infused obese rats within 1 week by modulating the impaired autonomic nervous control of different target tissues. This does not occur in lean rats.
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PMID:Central corticotropin-releasing factor administration prevents the excessive body weight gain of genetically obese (fa/fa) rats. 253 19

A high rate of lipogenesis in obese mice plays a major role in their excessive deposition of body lipid. Inhibition of lipogenesis may decrease their obesity. Therefore, we have investigated the effects of sodium 2-n-pentadecyl-benzimidazole-5-carboxylate (M & B 35347B), an inhibitor of acetyl-CoA carboxylase, on in-vivo lipogenesis in obese and lean mice. It significantly inhibited hepatic cholesterol and fatty acid synthesis, measured using 3H2O, in both lean and obese mice, with or without a glucose load. Brown adipose tissue (scapular) lipogenesis was decreased by M & B 35347B in obese mice but not in lean mice. In white adipose tissue, M & B 35347B did not affect the rates of lipogenesis in either scapular white, inguinal or epididymal depots of obese mice, or the inguinal and scapular white depot of lean mice. However, it doubled lipogenesis in the epididymal fat pad of lean mice. After a glucose load, lipogenesis in the lean epididymal fat pad was not inhibited but that in the inguinal depot was. M & B 35347B inhibited acetyl CoA carboxylase of adipose tissue in vitro but only a small inhibition was detected after in-vivo treatment. These different responses according to type of mouse, treatment and tissue site appear to stem from differences in inhibitor concentration and the importance of acetyl CoA carboxylase as the rate-limiting enzyme of lipogenesis. The weight gain of obese mice dosed orally (200 mg M & B 35347B/kg daily) for 60 days was unaffected and they continued to deposit excess body fat. This presumably occurred because of the lack of inhibition of fatty acid synthesis in white adipose tissue.
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PMID:Effect of sodium 2-n-pentadecyl-benzimidazole-5-carboxylate (M & B 35347B), an inhibitor of acetyl-CoA carboxylase, on lipogenesis and fat deposition in obese hyperglycaemic (ob/ob) and lean mice. 289 66

Adipsin expression at the protein and mRNA levels is greatly reduced in several distinct syndromes of obesity in the mouse: genetic obesity due to the db/db and ob/ob genes, and a chemically induced model secondary to neonatal exposure to monosodium glutamate. We considered first the possibility that the adipsin gene might be identical to the db or ob locus and the lowered expression of this protein might result from a mutation in this gene. We show here that the adipsin structural gene is located on chromosome 10 and hence is physically distinct from any obesity genes so far identified in the mouse. A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments. Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls. Exogenous administration of corticosterone completely blocks the effects of adrenalectomy on adipsin, suggesting that the effect of this endocrine ablation is through reduction of adrenal glucocorticoids. Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice. The effect of exogenous corticosterone in lean mice occurs within 2 days and hence is not secondary to the obesity which these hormones eventually elicit. These results indicate that glucocorticoids can regulate adipsin expression in vivo and strongly suggest that the hyperglucocorticoid state seen in certain obese models plays a significant role in lowering adipsin mRNA and protein levels. Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity.
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PMID:Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice. 291 85

In an attempt to determine the mechanism of insulin resistance in the presence of obesity, we examined effects of insulin on insulin-sensitive phosphodiesterase (PDE) in spontaneously diabetic KK mice. Isolated fat cells prepared from epididymal adipose tissue were incubated, with or without insulin, for 10 min. In the case of subcellular fractionation, only membrane-bound PDE was activated by insulin, as was noted in the case of rat fat cells. The specific activity was decreased in KK mice compared with control C57BL/6 mice. The dose-response curve, expressed as a percent of the maximal insulin effect, shifted to the right and the increase of ED50 indicated a decreased insulin sensitivity in the KK mice. The maximal insulin effect did not change, either when expressed as a percent of the basal enzyme activity or when expressed on a per cell basis. Specific binding of [125I]-insulin in fat cells increased in KK mice and curvilinear Scatchard plots showed an increase of the high-affinity sites. These data indicate that impairment of PDE activation in fat cells of KK mice relates to postreceptor defects and the uncoupling may result in a decreased sensitivity.
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PMID:Insulin resistance of fat cells from spontaneously diabetic KK mice. Analysis of insulin-sensitive phosphodiesterase. 299 83

Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was sustained as long as the drug was administered. The hypolipidemic effect of MEDICA 16 consisted of a 70 and 40% decrease in plasma triacylglycerols and cholesterol, respectively, and resulted from inhibition of liver lipogenesis and cholesterogenesis. Adipose reduction by MEDICA 16 treatment or calorie restriction consisted of a 75-90% decrease in the perirenal, omental, epididymal, and subcutaneous fat, with a 50% decrease in liver neutral lipids. The reduction in adiposity was accounted for by a respective decrease in the lipid content of individual adipocytes, with a concomitant decrease in the number of adipocytes of selected adipose tissues. The decrease induced in adiposity by MEDICA 16 treatment could not be accounted for by anorectic or cathartic effects of the drug. The hypoglycemic-hypoinsulinemic effect of MEDICA 16 consisted of amelioration of the tolerance of glucose with normalization of plasma insulin. It was accompanied by an eightfold increase in the number of insulin receptors in epididymal adipocytes, which was, however, counteracted by a decrease in their affinity for insulin. The receptor and postreceptor effects exerted by MEDICA 16 were similar to those of calorie restriction. The overall effect of MEDICA 16 in sand rats may reflect the pharmacological potential of MEDICA compounds in pathological hyperlipidemic-obesity-diabetic syndromes.
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PMID:Hypolipidemic, antiobesity, and hypoglycemic-hypoinsulinemic effects of beta,beta'-methyl-substituted hexadecanedioic acid in sand rats. 305 60

Male Long-Evans rat pups were either fed by continuous intragastric infusion of a milk formula to match the growth rate of their normally reared siblings, or overfed by continuous infusion of a fat-supplemented formula from d 4 through d 18 postpartum. The early overfeeding accelerated growth and the overfed rats remained significantly heavier than normally reared siblings as adults. Early overfeeding with this procedure led to an adult obesity at 14 mo characterized by significantly larger epididymal and retroperitoneal fat depots resulting from an increase of both fat cell size and number, and by an increase in adipose tissue lipoprotein lipase activity. Gastrostomy rearing per se, without overfeeding, resulted in adult rats that weighed the same as normally reared siblings but had significantly larger retroperitoneal fat depots because of more adipocytes. These findings suggest that the quantity of food consumed during early growth and development, and the quality of early nutrition and/or the early rearing environment affect adipose tissue development and have long-term consequences that persist in the rat.
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PMID:Long-term effects on adiposity after preweaning nutritional manipulations in the gastrostomy-reared rat. 311 35

Obesity was induced in neonatal mice by subcutaneous injections of monosodium glutamate (MSG) at an early neonatal stage. The process of adipocyte formation was studied comparatively in the developing epididymal adipose tissue of the MSG-treated mice and in normal mice during the period from the 6th to the 100th postnatal day. Tritiated thymidine autoradiographic studies showed that cell proliferation activity was the highest on the 6th postnatal day both in the MSG-treated and the control mice. In normal mice, however, cell proliferation took place less frequently after 6 days and had almost ceased after 49 days. In the obese mice, as evidenced by relatively high labeling indices, cell proliferation continued to occur even after 49 days. Ultimately there was no difference in the number of adipocytes counted by Hirsch's method in the MSG-treated and the control mice at the 100th postnatal day. The storage of fat droplets became more noticeable in obese mice than in normal mice after 35 days. The mean size of fat droplets of the obese mice was twice as large as that in normal mice on the 49th postnatal day. These results indicate that the MSG-induced obesity is of the hypertrophic type.
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PMID:Development of the epididymal adipose tissue in monosodium glutamate-induced obese mice. 318 80


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