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

By employing neutron activation analysis, endogenous content of gold was estimated quantitatively in discrete brain areas and in subcellular fractions of the hypothalamus of gold thioglucose (GTG) induced obese mice. The highest concentration of gold was obtained in the ventromedial hypothalamus (VMH) reaching approximately 100 ng/mg wet tissue. Significantly higher concentrations were observed in other hypothalamic subareas followed by certain limbic areas and the thalamus, while in the cerebral and the cerebellar cortex the gold concentration was very low. Subcellularly, the hypothalamic gold was principally recovered in the supernatant fraction particularly after a hyposmotic shock treatment of the crude mitochondrial fraction. Contrary to GTG, treatment with gold thiomalate (GTM) did not induce obesity in the mouse, although considerable amount of gold was observed in the VMH, a finding suggesting the existence in the VMH of at least a two step mechanisms for inducing GTG obesity. To identify the satiety neuron transmitter, an analysis of certain enzyme activities involved in the synthesis of known transmitters, such as acetylcholine or gamma-aminobutyric acid (GABA), was made in the GTG-obese mice. There were no significant changes in any of the areas functionally related to the VMH.
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PMID:Regional and subcellular distribution of gold in brain of gold thioglucose obese mouse. 10 Dec 85

To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.
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PMID:Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats. 132 68

Studies were conducted to determine whether metabolic adaptation occurred in the hypothalamus of overfed parabiotic rats and their partners to distinguish between the adaptations caused by increased caloric intake and those caused by the production of a "lipostatic factor." The induction of overfed obesity in one parabiotic partner was employed to test the hypothesis that a putative lipostatic factor produced in the obese parabiotic elicited the hypophagic-lipid-mobilizing effect observed in the lean parabiotic via alterations in hypothalamic fatty acid and glucose metabolism. Fatty acid oxidation in the ventrolateral hypothalamus (VLH) of overfed parabiotic rats and their partners was lower than in ad libitum parabiotic rats. Net flux of glucose through the VLH gamma-aminobutyric acid (GABA) shunt was elevated in overfed parabiotic rats compared with the net flux observed in their partners and ad libitum parabiotic rats, the levels being similar in these last two groups. Net flux of glucose through the ventromedial hypothalamic (VMH) pentose shunt in overfed parabiotic rats and their partners was elevated relative to ad libitum parabiotic rats. The putative lipostatic factor may act to regulate energy balance through modification of VLH fatty acid oxidation and/or glucose flux via the VMH pentose shunt.
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PMID:Site of action of putative lipostatic factor: hypothalamic metabolism of parabiotic rats. 254 57

Whole brain concentrations of 3-hydroxybutyrate, glutamate and gamma-aminobutyric acid (GABA) have been measured in two strains of rats with differing susceptibility to obesity. S 5B/Pl rats are resistant to developing obesity when eating a high-fat diet, whereas Osborne-Mendel rats readily develop obesity when eating the same diet. We tested the hypotheses that brain 3-hydroxybutyrate, glutamate and GABA differ between S 5B/Pl rats and Osborne-Mendel rats, and that these substrates/neuroregulators are altered when eating a high-fat diet primarily in S 5B/Pl (resistant) rats. Blood and brain 3-hydroxybutyrate concentrations were higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.05) but diet effects were not significant. Brain glutamate concentration, like 3-hydroxybutyrate, was higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.01) and was not affected by adding fat to the diet. Brain GABA differed only slightly between strains but increased after adding fat to the diet (p less than 0.05) in both strains with a greater increase occurring in S 5B/Pl rats. The brains of S 5B/Pl rats are chronically exposed to higher levels of 3-hydroxybutyrate and glutamate than are those of Osborne-Mendel rats. Thus, 3-hydroxybutyrate is a potential signal in the regulation of body weight. Brain GABA increases with fat feeding, especially in S 5B/Pl rats, suggesting that the ability to adjust to an energy dense diet may be through suppression of food intake by elevated brain GABA.
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PMID:Brain 3-hydroxybutyrate, glutamate, and GABA in a rat model of dietary obesity. 266 5

Metabolic signals have been proposed as controls of energy balance. Glucose utilization for gamma-aminobutyric acid (GABA) synthesis was evaluated in diet-restricted and streptozotocin-diabetic rats. Rates for glucose flux through the GABA shunt and glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis, were measured in ventro-medial nucleus (VMN) and lateral hypothalamic (LHA) homogenates. Rates of GAD activity were elevated in the VMN of both restricted and diabetic rats but did not change in the LHA of either model. The rate of glucose flux through the GABA shunt in the VMN was increased in restricted rats but were decreased in the VMN of diabetic rats. Restricted rats allowed to feed ad libitum initially ate 160% of the amount the control rats ate. GAD activity rates in the VMN returned to near control levels after 2 days of refeeding. Obese Zucker rats (fa/fa) also had higher rates of GAD activity and glucose flux through the GABA shunt in the VMN but not in the LHA. The increased rate of GABA synthesis may represent increased GABAergic activity in the VMN and may possibly be involved in feeding behavior and energy balance.
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PMID:Increased GABA shunt activity in VMN of three hyperphagic rat models. 273 48

A variety of recent literature suggests that brain gamma-aminobutyric acid (GABA) plays an important role in the control of feeding. One such line of evidence is that pharmacological inhibition of brain GABA transaminase (GABA-T) produces dose-dependent anorexia in otherwise normal rats. To determine the generality of these findings we tested the ability of the GABA-T inhibitor ethanolamine-O-sulfate (EOS), to produce anorexia in three animal models of obesity: rats with medial hypothalamic lesions, rats exposed to palatable foods or Zucker fatty rats. Following intracisternal injection of 100, 200 or 400 micrograms EOS, all three models of chronic overeating showed dose-dependent anorexia of similar magnitude and duration to that seen in appropriate controls. These observations provide empirical support for previous suggestions that treatments which enhance brain GABA neurotransmission merit investigation for their potential use in treating excess energy consumption.
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PMID:Anorectic potency of inhibiting GABA transaminase in brain: studies of hypothalamic, dietary and genetic obesities. 653 93

1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered in obese (fa/fa) Zucker rats, plays an important role in controlling energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms in these animals due to a genetically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam) lowered insulin concentration in obese rats. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clarify the pathophysiology of obesity and insulin resistance in fatty Zucker rats.
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PMID:Influence of benzodiazepines on body weight and food intake in obese and lean Zucker rats. 1095 51

The injection of a melanocortin peptide or of melanocortin peptide analogues into the cerebrospinal fluid or into the ventromedial hypothalamus in nanomolar or subnanomolar doses induces a long-lasting inhibition of food intake. The effect keeps significant for up to 9 h and has been observed in all animal species so far tested, the most susceptible being the rabbit. The anorectic effect of these peptides is a primary one, not secondary to the shift towards other components of the complex melanocortin-induced behavioral syndrome, in particular grooming. The site of action is in the brain, and the effect is not adrenal-mediated because it is fully exhibited also by adrenalectomized animals. It is a very strong effect, because the degree of feeding inhibition is not reduced in conditions of hunger, either induced by 24 h starvation, or by insulin-induced hypoglycemia, or by stimulation of gamma-aminobutyric acid (GABA), noradrenergic or opioid systems. The microstructural analysis of feeding behavior suggests that melanocortins act as satiety-inducing agents, because they do not significantly modify the latencies to start eating, but shorten the latencies to stop eating. The mechanism of action involves the activation of melanocortin MC(4) receptors, because selective melanocortin MC(4) receptor antagonists inhibit the anorectic effect of melanocortins, while inducing per se a strong stimulation of food intake and a significant increase in body weight. Melanocortins seem to play an important role in stress-induced anorexia, because such condition, in rats, is significantly attenuated by the blockage of melanocortin MC(4) receptors; such a role is not secondary to an increased release of corticotropin-releasing factor (CRF), because, on the other hand, the CRF-induced anorexia is not affected at all by the blockage of melanocortin MC(4) receptors. The physiological meaning of the feeding inhibitory effect of melanocortins, and, by consequence, the physiological role of melanocortins in the complex machinery responsible for body weight homeostasis, is testified by the hyperphagia/obesity syndromes caused by mutations in the pro-opiomelanocortin (POMC) gene, or in the melanocortin MC(4) receptor gene, or in the agouti locus. Finally, recent evidences suggest that melanocortins could be involved in mediating the effects of leptin, and in controlling the expression of neuropeptide Y (NPY).
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PMID:Role of melanocortins in the central control of feeding. 1103 11

Transgenic mice ubiquitously overexpressing murine gamma-aminobutyric acid transporter subtype I were created. Unexpectedly, these mice markedly exhibited heritable obesity, which features significantly increased body weight and fat deposition. Behavioral examination revealed that transgenic mice have slightly reduced spontaneous locomotive capacity and altered feeding pattern. This preliminary finding indicates that the inappropriate level of gamma-aminobutyric acid transporters may be directly or indirectly involved in the pathogenic mechanism underlying certain types of obesity.
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PMID:Transgenic mice overexpressing gamma-aminobutyric acid transporter subtype I develop obesity. 1119 52

The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (gamma-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus.
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PMID:Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. 1137 81


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