Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.
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PMID:Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. 903 86

To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH-lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH-lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single i.v. (1.0 mg/rat) or intracerebroventricular (2.0 micrograms/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH-lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.
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PMID:Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats. 904 94

To explore the pathophysiologic roles of the obese (ob) gene product, leptin, in the development of obesity and hypertension, we examined ob gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats) at the stage of established obesity and hypertension. Expression of the ob gene was augmented in the epididymal, mesenteric, subcutaneous, and retroperitoneal white adipose tissue (WAT) from 20-week-old male obese SHR compared to their lean littermates (lean SHR). Using a radioimmunoassay for rat leptin, we also measured plasma leptin levels in 20-week-old lean and obese SHR. Plasma leptin levels in obese SHR (292.5 +/- 37.1 ng/ml) were more than 100-fold higher than those in lean SHR (2.8 +/- 1.0 ng/ml). The present study demonstrates that ob gene expression and leptin secretion are markedly augmented in obese SHR.
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PMID:Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats). 907 Aug 50

In male Wistar rats the influences of age and experimental obesity on the activity of malic enzyme (EC 1.1.1.40) in different organs were studied. Obesity was induced in newborn rats by injection of Na(+)-L-glutamate (2 mg/g b.w. daily) subcutaneously in the first 5 days. The enzyme activity was measured at the ages of 2, 6 and 18 months. In control animals the highest enzyme activities were found in the heart muscle, liver, epididymal fat pad and skeletal muscle after 6 months. After 18 months the activities in these organs are considerably reduced. In the kidneys the activity between the 2nd and the 18th months tends to decrease continuously and only the brain shows an opposite trend. In comparison with the control animals, in glutamate treated rats the enzyme activity doubles nearly in the lipogenic organs liver and fat tissue in all age groups. In liver and fat tissue of 6-month-old rats, previously treated with clonidine to stimulate growth hormone secretion, the activities are lower than in glutamate obese rats without clonidine, but still higher than in normal control animals. The qualification of glutamate obese rats as a model for the study of age-associated diseases like obesity or diabetes mellitus type II needs further investigation.
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PMID:[Obesity, malic enzyme and aging--an animal experiment study]. 908 41

1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic activity, admixed in a pellet diet was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%) suppressed bodyweight gain without affecting food and water consumption until the appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in control rats, and in rats fed a low (0.002%) and high dose of carteolol, respectively). 2. At the 26th week of administration, the high dose of carteolol decreased visceral fat weight, such as that of retroperitoneal and epididymal adipose tissue, whereas the liver and the kidney were not affected. 3. Although plasma glucose and triglyceride levels in non-fasted rats were elevated with age, carteolol tended to delay the increases in those parameters. Carteolol suppressed the increase in plasma glucose levels, which indicate the diabetic pattern, in a 25th week oral glucose tolerance test. 4. These findings indicate that carteolol induces improvements in bodyweight and carbohydrate and lipid metabolism in an obese condition. Consequently, carteolol may be useful for the treatment of hypertension with obesity in order to prevent cardiovascular events.
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PMID:Improving effect of carteolol on bodyweight and carbohydrate and lipid metabolic responses in the OLETF rat. 914 81

To clarify whether a beta(3)-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities of 0, 1 and 10,000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150 g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific beta-adrenoceptor agonist, isoproterenol, and by the beta(3)-specific adrenoceptor agonist, CL316,243, but the lipolytic sensitivity to CL316,243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316,243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD2 value [-log mol l-1 for EC50 (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316,243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316,243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.
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PMID:Effect of CL316,243, a highly specific beta(3)-adrenoceptor agonist, on lipolysis of epididymal, mesenteric and subcutaneous adipocytes in rats. 915 32

Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced immunoregulator. A survey of tissue distribution revealed that MIF expression is not limited to T lymphocytes, but exists in several other tissues; however, its presence in adipose tissue has never been investigated. In this study, we examined the expression of MIF in adipose tissue using the rat epididymal fat pad and murine 3T3-L1 adipocytes. Northern and Western blot analyses revealed the expression of MIF mRNA and MIF protein, respectively, in both the fat pad and the adipocyte cell line. In immunohistochemistry, a positive staining reaction with an anti-rat MIF antibody was detected largely in the cytosol of adipocytes of the epididymal fat pad. To examine the production and release of MIF by adipocytes, we examined its content in the culture medium of the 3T3-L1 adipocytes. The results showed that MIF content was 1.6 +/- 0.48 ng/ml (mean +/- SD) after 24 hr culture, and the content was increased up to 9.7 +/- 2.8 ng/ml by stimulation with TNF-alpha (50 nM). Since TNF-alpha produced in adipocytes is known to induce insulin resistance, the results suggest the possibility that MIF plays an important role in the mechanism of insulin resistance often observed in obesity and diabetes via regulation of TNF-alpha expression.
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PMID:Identification of macrophage migration inhibitory factor in adipose tissue and its induction by tumor necrosis factor-alpha. 919 42

The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.
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PMID:Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats. 920 Jun 51

High levels of adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) mRNA and protein have previously been associated with genetic models of obesity and insulin resistance. Because there are endogenous TNF inhibitors it is unknown if AT-TNF activity is also increased. We hypothesized that AT-TNF activity would increase in older animals because of an accumulation of fat mass. We chose to study 2 different-aged male Fischer 344 rats, 3-month-old (young) and 14-month-old (mature) because fat mass should be quite different but insulin action on glucose metabolism similar. Indeed, mature rats had over 1.5-fold more fat mass, but whole body insulin resistance, as estimated by fasting plasma insulin, was similar to young rats. Mature rats had twice as much AT-TNF activity as the young in both the epididymal (EPI) and retroperitoneal (Retro) fat pads (p < .0005). AT-TNF correlated with fasting plasma insulin in Retro only (r = .48, p = .04). AT-TNF activity strongly correlated with cell size in both EPI and Retro (r = .79 and .81, respectively, p < .0001). Because cytokines can be regulated at several levels, AT-TNF activity, protein, and mRNA were measured. AT-TNF protein levels were higher in young rats, suggesting that these animals may secrete an inhibitor that reduces AT-TNF activity. There were no significant differences in AT-TNF mRNA between groups. Since TNF has been shown to affect several key genes in tissue culture, mRNA for lipoprotein lipase, hormone-sensitive lipase, and Glut4 were measured. No differences were found between groups. In summary, AT-TNF activity increased in mature animals in relation to adipose cell size.
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PMID:Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats. 922 23

Administration of the murine-selective beta3 adrenoceptor agonist CL-316,243 corrects obesity and elevated blood glucose in diabetic rodents. This antiobesity effect is attributed to an increase in the thermogenic activity of brown adipose tissue (BAT). The antidiabetic effect is unknown, but has been attributed to the decline in body weight and plasma free fatty acids (FFAs). This study using the euglycemic-hyperinsulinemic clamp method was performed in nonobese, nondiabetic Sprague-Dawley rats fed normal rodent chow to determine if the beta3 agonist could improve insulin sensitivity and/or responsiveness in the absence of weight loss or lowering of circulating FFAs. Subcutaneous miniosmotic pumps delivered either saline to control or 1 mg x kg(-1) x day(-1) of CL-316,243 for 10-12 days. Fed plasma glucose, insulin, and FFA levels were similar between the groups. Significant increases in food consumption, resting metabolic rates, and body core temperatures occurred, but only after 7 days of treatment. A 14% decrease in the respiratory quotient was also observed. Plasma glucose and insulin excursions in response to an oral glucose load (2 g/kg) on day 11 were unaltered. Cl-316,243 treatment resulted in a decrease in abdominal and epididymal white fat pad weights, while interscapular brown adipose tissue (IBAT) weight doubled. Basal and insulin-stimulated whole-body glucose disposal rates were increased, while hepatic glucose output was suppressed to a greater extent in the CL-316,243 animals after 10 days of uninterrupted treatment. Chronic treatment with CL-316,243 resulted in an increase in basal and insulin-stimulated [3H]2-deoxyglucose (2-DG) uptake by the retroperitoneal and epididymal white tissue and IBAT, but skeletal muscle 2-DG uptake under the same conditions was unaltered. These studies demonstrate that treatment with CL-316,243 improves basal and insulin-stimulated glucose disposal, and these effects occurred in the absence of a decrease in body weights and FFA concentrations. A particularly interesting observation was that the tissues responsible for this effect were white and brown adipose tissue, while skeletal muscle remained unaffected.
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PMID:CL-316,243, a beta3-specific adrenoceptor agonist, enhances insulin-stimulated glucose disposal in nonobese rats. 923 48


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