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

Several lines of evidence support the hypothesis that derangements in the function of the autonomic nervous system play an important role in the development of hypothalamic obesity. Vagotomy below the diaphragm reverses the syndrome. In diabetic rats cured of their diabetes with transplants of fetal pancreatic tissue beneath the renal capsule, ventromedial hypothalamic (VMH) lesions do not produce the characteristic rise in food intake nor do they significantly increase serum insulin. These observations indicate that the hyperinsulinaemia following VMH lesions is the result of neural connections rather than from a circulating humoral factor released following VMH injury. The smaller salivary glands, reduced level of glucagon and impaired mobilization of fatty acids during stress in VMH lesioned rats point to reduced activity of the sympathetic nervous system. The impaired mobilization of fat from retroperitoneal depots in VMH lesioned rats during fasting is similar to the effect of sympathetic denervation of the retroperitoneal fat pad. The turnover of norepinephrine in tissues innervated by the sympathetic nervous system is either reduced or less responsive to nutritional influences after VMH lesions. The thermogenic activity of brown adipose tissue is also impaired after VMH lesions, presumably as a result of reduced sympathetic firing rate of nerves innervating the BAT. In contrast to the reduced activity of the sympathetic nervous system after Vmh lesions there is increased activity after electrolytic lesions of the lateral hypothalamus. Collectively these data indicate that the autonomic nervous system plays a central role in the regulation of metabolic functions following disturbances of hypothalamic function. The concept of the thrifty gene as a mechanism for the development of obesity has been explored in several models. The efficiency with which food is stored as fat appears to be increased in all forms of experimental obesity. Studies in the genetically obese mouse have documented this phenomenon most elegantly. In one experiment animals carrying a double dose of the gene for obesity received exactly the same quality of food on exactly the same schedule throughout a 24 hour period of time as their lean littermates yet gained more body weight and more fat. In a second experiment the importance of a thrifty gene was documented by comparing the rates of weight loss and survival time in homozygous and heterozygous lean animals. Heterozygosity improved survival compared to the homozygous lean animal indicating the value of the genetic trait for survival in the wild.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypothalamic and genetic obesity: an appraisal of the autonomic hypothesis and the endocrine hypothesis. 639 3

Obese rats with lesions of the ventromedial hypothalamus (VMH) exhibited a 3-fold increase in the wet weight of interscapular brown adipose tissue (IBAT), due to an increased triglyceride content, compared with lean controls. The rate of lipogenesis in IBAT was much higher than that in white adipose tissues in control rats, but decreased greatly in rats with VMH lesions and approximated the value in white adipose tissues. It was suggested that thermogenesis in BAT was impaired after VMH lesions by decreasing triglyceride turnover in BAT.
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PMID:Decreased rate of fatty acid synthesis in brown adipose tissue of hypothalamic obese rats. 669 18

The past 10-15 years have produced a significant increase in knowledge and theories concerning the regulation of energy balance, but the precision of this regulation is still uncertain. However, the fact that investigators have had to resort to a variety of techniques and ploys (some of them bizarre) to produce marked pertubations in body weight is in itself an indication that the regulatory system can be very robust. Although control of food intake obviously plays a major role in this system, control of energy expenditure (i.e. DIT) also has to be considered as an important factor in the maintenance of energy balance. In this review most of the evidence for DIT and its biochemical origins has been derived from studies on experimental animals. Many of the overfeeding studies carried out on man are consistent with the animal work, but because of differences in interpretation and some equivocal results, the role of DIT in human metabolism is still a contentious issue. This problem may not be fully resolved to everyone's satisfaction until complete, continuous, and very precise energy balance measurements are made on chronically overfed lean subjects. Before this expensive and arduous experiment is undertaken, evidence for thermogenesis in man will continue to depend on acute measurements of the metabolic response to various stimuli. An increasing number of studies (e.g. 35, 80) have demonstrated the existence of NST in man, and the possibility that this could originate from BAT is supported by histological (62, 148) and thermographic data (130). Conversely, reductions in cold tolerance (2, 18) and thermogenic responses to noradrenaline (82) with increasing adiposity are similar to the blunted responses seen in genetically obese animals, which suggests that human obesity may also involve an impairment in thermogenesis. At the present time these ideas concerning the important of DIT in man and its role in obesity remain somewhat speculative, but no doubt this area will now be the subject of further research. Similarly, the impact of early nutritional influences on subsequent energy balance regulation and resistance to obesity will receive more attention following the report (144) that hyperphagia in rats during early life results in a reduced body fat content and leanness in adulthood. The relative contributions and interactions between intake and output in energy balance need clarifying, and in terms of central organization, the mechanisms of appetite control should now be considered for their relevance to the control of thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of energy balance. 676 16

Certain aspects of intermediary metabolism of white (epididymal) and brown (interscapular) adipose tissue (BAT) were studied in cold-acclimated weanling rats with hypothalamic obesity. Groups of rats with ventromedial hypothalamic lesions (VMNL rats) and controls were maintained for four weeks at 6 degrees C and 22 degrees C, respectively. Sham-operated rats served as controls. Cold-acclimated VMNL rats showed greater percent BAT but normal percent epididymal fat pad weight, hypophagia, reduced body weight and body weight gains, hyperdipsia, hyperinsulinemia, normoglycemia and normal circulating fatty acid levels, higher carcass lipid and lower carcass protein. They also exhibited a higher rate of epididymal fat pad lipolysis than the controls, but the increment during cold adaptation was less in the VMNL rats compared with the 22 degrees C-maintained VMNL animals. In-vitro metabolism was determined in both the basal and the epinephrine-stimulated state. Basal-state 14C-palmitate oxidation, BAT fatty acid and lipid contents were increased in VMNL rats but protein content, incorporation into phospholipid and triglycerides, BAT lipolysis and glycolysis were normal in cold-acclimated VMNL rats. Epinephrine-stimulated BAT showed similar fatty acid content and palmitate oxidation and incorporation into triglycerides in VMNL and control rats. Epinephrine-stimulated BAT showed similar fatty acid content and palmitate oxidation and incorporation into triglycerides in VMNL and control rats, but the epinephrine-stimulated increase in lipolysis only in the cold-acclimated VMNL rats. Whereas at 22 degrees C BAT of VMNL rats showed decreased palmitate oxidation and no change of incorporation into phospholipid and triglyceride, during cold acclimation VMNL rats showed normal BAT metabolism and normal response to epinephrine, except for an increase in lipolysis. The data are in agreement with the observation that hypothalamic-obese mature rats have normal cold survival potential and allow us to extend this fact to the normophagic-obese-weanling rat.
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PMID:Brown adipose tissue metabolism in cold-acclimated weanling rats with hypothalamic obesity. 688 32

The aim of this study was to determine if the previously described insulin resistance in the New Zealand Obese (NZO) mouse is associated with a decrease in GLUT4 protein and if such changes occur early in the evolution of the syndrome. GLUT4 levels were measured in whole membranes isolated from a variety of tissues in 4 and 20-week-old NZO and control NZC mice by Western blotting using a specific antibody to the C terminal end of the protein. At 20 weeks of age, GLUT4 levels were lower in the NZO mice in brown and white adipose tissue, heart, diaphragm, red and white quadriceps, and red and white gastrocnemius, but not in soleus muscle. At 4 weeks of age, GLUT4 levels were 52% lower in BAT (3309 +/- 1006 vs 6951 +/- 1870 cpm P = 0.039) but were not lower in WAT, heart or red quadriceps. It is concluded that adult NZO mice have a decrease in GLUT4 levels in most insulin-sensitive tissues and that in BAT, this occurs at an early age.
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PMID:Early decrease in GLUT4 protein levels in brown adipose tissue of New Zealand obese mice. 786 77

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

The objective was to determine the effects of persistent obesity on amino acid enzymes in white (WAT) and brown (BAT) adipose tissues. Dietary obesity was induced by feeding a cafeteria diet ad libitum for 3 months, then it was removed and the obese animals received the same diet as controls for 5 months. Dietary-induced obesity was persistent as obese rats showed a stable, higher body weight than controls (26%). Key enzymes of alpha-amino nitrogen metabolism were studied and results showed reduced activities in obese rats: glutamine synthetase (45%), AMP deaminase (52%), alanine aminotransferase (66%) and glutamate dehydrogenase (68%) in BAT, whereas WAT of obese animals only showed lower aspartate aminotransferase activity (47%) with respect to the controls. We can conclude that these adaptations in amino acid metabolism were exclusively dependent on the obese status as they were observed in an obesity model in which obese rats eat the same diet as controls.
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PMID:Brown and white adipose tissue adaptive enzymatic changes on amino acid metabolism in persistent dietary-obese rats. 791 90

This study was undertaken to determine whether acute injection of the beta-adrenoceptor BRL 35135, which is known to activate thermogenesis, could correct the earliest detectable metabolic abnormalities that characterize brown (BAT) and white (WAT) adipose tissues of pre-obese Zucker rats. In 14-day-old pups, a single intraperitoneal injection of BRL (10 micrograms/g, 3 h before sacrifice) had no effect on uncoupling protein mRNA content in BAT of lean pups, whereas the low level of this mRNA was restored to normal in pre-obese rats. Both lipoprotein lipase (LPL) activity and mRNA content, which were decreased in BAT of pre-obese compared to lean pups (-60%), were stimulated after BRL injection. However, this effect was more pronounced in fa/fa than in Fa/fa rats (+100% and +50%, respectively). In BAT, the increase in fatty acid synthetase (FAS) activity observed in fa/fa rats compared to their lean Fa/fa littermates was not reduced. In WAT, the stimulation of beta-adrenergic receptors had no effect on lipid storage capacity, since FAS and LPL activities remained unchanged. In conclusion, pre-obese Zucker fa/fa rats are responsive to BRL 35135 treatment: acute administration of this drug was able to improve impaired thermogenesis and to correct temporarily other abnormalities of early emergence in BAT. This treatment had no effect in WAT. Taken together, our data reinforce the hypothesis that reduced sympathetic activity in BAT is one of the primary lesions of the obese rat which may play a key role in the development of this genetic obesity.
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PMID:Acute injection of beta-adrenoceptor agonist BRL 35135 corrects both impaired uncoupling protein and lipoprotein lipase gene expression but not hypercapacity of lipogenesis in brown adipose tissue of suckling fa/fa rats. 791 94

Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis. The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis. We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue. Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein. UCP3 RNA levels are regulated by hormonal and dietary manipulations. In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation. In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased 6-fold in hyperthyroid rats. Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis. UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation. The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity.
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PMID:Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. 930 58

Neuropeptide Y (NPY) potently induces feeding, reduces thermogenesis and induces obesity in rats when injected into the cerebral ventricles. Groups of male Wistar rats were either restricted to 60% of their normal daily food intake over 10 days or made obese by presenting them with a high-calorie diet rich in sugars and fat over 6 weeks. Food restricted rats lost up to 20% of their body weight, compared with control rats and had large reductions in their body fat mass. By contrast, rats with dietary-induced obesity weighed 26% more than controls due mainly to increased body fat mass. Quantitative receptor autoradiography demonstrated reduced [(125)I]PYY binding in the hypothalamic lateral (perifornical) and dorsal areas, hypothalamic ventromedial, arcuate and dorsomedial nuclei, hippocampal CA3 region, centromedial amygdaloid nucleus and thalamic paraventricular and reuniens nuclei in dietary restricted rats compared with controls. By contrast, regional [(125)I]PYY binding was significantly increased in hypothalamic lateral and dorsal areas, hypothalamic arcuate and dorsomedial nuclei, amygdaloid medial and centromedial nuclei, thalamic centromedial and paraventricular nuclei of dietary obese rats versus controls. Masking NPY Y1 receptors with 1 microM BIBP3226, a selective Y1 receptor antagonist, revealed that the changes in [(125)I]PYY binding in brains of food-restricted and dietary-obese rats were due to changes in BIBP3226-insensitive binding sites, presumably Y2 or Y5 NPY receptors. These data suggest that dietary-restriction stimulates NPY release resulting in down-regulation of NPY Y5 'feeding' and/or Y2 receptors and reduced BAT thermogenesis thereby providing an increased drive to eat to restore normal caloric intake whilst reducing thermogenesis in order to conserve fat reserves. By contrast, the up-regulation of NPY Y5 and/or Y2 receptors in dietary-induced obesity is consistent with inhibition of NPY release in the hypothalamus, amygdala and thalamus. Overall, we suggest that there is a regional increase in NPY release during negative energy balance, such as during food-restriction and a reduced regional release of NPY in positive energy balance, such as during hyperphagia associated with the development of obesity.
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PMID:Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat. 945 85


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