Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Past literature is reviewed briefly which suggests that variations in brain GABA metabolism may be involved in the control of food intake in rats. Recent experiments from the author's laboratory are summarized in which brain GABA has been elevated in adult female rats by intracisternal injection of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS). Central EOS pretreatment produced dose-dependent anorexia in normal subjects and prevented acute overeating in response to systemic insulin (12 U/kg) or 2-deoxyglucose (750 mg/kg). Similar EOS pretreatment essentially reversed the chronic overeating induced by diet palatability, bilateral medial hypothalamic lesions or genetic predisposition (in Zucker fatty rats). The ubiquity of these anorexic effects in the absence of clear motor debilitation suggests that drugs which elevate brain GABA deserve further investigation for their potential utility in the clinical treatment of overeating.
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PMID:GABA and feeding: reversal of overeating by central GABA-transaminase inhibition. 668 89

Acute feeding responses to 2-deoxyglucose (750 mg/kg) or insulin (12 U/kg) were examined 24 hr after intracisternal injection of the GABA-transaminase inhibitor ethanolamine-O-sulfate (EOS, 400 micrograms) in female rats. EOS pretreatment completely abolished acute feeding responses to both challenges. These findings complement recent research showing that central EOS can reverse chronic overeating in several experimental preparations. The present results are consistent with previous indications that EOS treatment may induce a metabolic shift away from brain glucose utilization, thus making glucoprivation irrelevant as a metabolic challenge. An alternative possibility is that EOS-induced increases of brain GABA may offset specific neural mechanisms through which these glucoprivic agents normally induce feeding.
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PMID:Inhibition of acute feeding responses to systemic 2-deoxyglucose or insulin in rats pretreated with the GABA-transaminase blocker ethanolamine-O-sulfate (EOS). 676 11

The metabolic effects of intravenous hyperalimentation, using an essential amino acid (EAA) and glucose solution, were evaluated in 2 children with acute renal failure. Hyperammonemia and hyperchloremic metabolic acidosis associated with elevated plasma methionine and depressed plasma citrulline, ornithine, arginine, and histidine levels complicated the nutritional therapy. Initial infusion of a complete amino acid (CAA) solution was not associated with these aberrations and reintroduction of a CAA solution after the EAA trial resulted in a progressive amelioration of or complete recovery from these metabolic disturbances. It is likely that the hyperammonemia was due to an arginine deficiency, while excess methionine and presumably sulfate production may have contributed to the hyperchloremic metabolic acidosis in these two children.
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PMID:Complications of essential amino acid hyperalimentation in children with acute renal failure. 676 49

Total parenteral nutrition (TPN) is a clinical adjunct to cancer therapy. But it is difficult to do controlled clinical studies on cancer patients undergoing TPN. We therefore turned to a study of TPN on Buffalo strain rats with and without a Morris 7777 transplantable hepatoma. Our results showed that TPN at higher than normal levels (total parenteral hyperalimentation, abbreviated TPH) supported a gain in body weight of nontumorous rats. In tumorous rats, TPH supported body weight gain and stimulated tumor growth. Detailed analysis showed the TPH of the rats with a large rapidly growing hepatoma did gain body weight associated with fluid retention while the carcass weight decreased. Nor did TPH of tumorous rats significantly reverse the low cell proliferative activity to ear epidermis attributed to the tumor though it did stimulate tumor cell proliferation. Thus TPH by itself did not overcome wasting due to presence of the tumor. Using the hypothesis that uncontrolled gluconeogenesis is linked to cancer cachexia, we combined TPH with inhibition of gluconeogenesis (using hydrazine sulfate) and prevented the carcass weight loss (cachexia) in the tumorous rats. Tumor growth was stimulated by this treatment. Stimulation of cell proliferation in the tumor can, however, benefit chemotherapy using an S phase or cell cycle-specific cytotoxic drug.
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PMID:Effect of total parenteral nutrition on tumor-host responses in rats. 680 28

This work expands recent observations that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no pancreatic expression of the cholecystokinin (CCK)-A receptor gene. We examined whether the CCK-A and -B receptor genes were expressed in the brain (hypothalamus) of OLETF rats in comparison with control (Long-Evans Tokushima Otsuka = LETO) rats. CCK-A receptor mRNA was detected in the hypothalamus of LETO rats but not OLETF rats. The CCK-B receptor gene was expressed in the hypothalamus in both strains. Cerebroventricular administration of CCK-8 sulfate inhibited daily food intake in LETO rats, but not in OLETF rats. These results show that in OLETF rats the absence of CCK-A receptor gene expression in the hypothalamus results in hyperphagia because of lack of satiety.
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PMID:Lack of satiety effect of cholecystokinin (CCK) in a new rat model not expressing the CCK-A receptor gene. 770 May 67

Cancer anorexia/cachexia is a common clinical problem that substantially impacts upon the quality of life and survival of affected patients. Extensive investigations have not supported the use of either enteral or paternal hyperalimentation for such patients. Despite positive pilot trial reports, large randomized studies have been unable to demonstrate a clinically defensible role for either pentoxifylline, cyproheptadine, or hydrazine sulfate for patients with anorexia. Multiple placebo-controlled, randomized, double-blind, clinical trials have demonstrated that corticosteroids do have appetite-enhancing properties in patients suffering from cancer anorexia/cachexia, but none of these studies has demonstrated weight gain. In comparison, multiple studies have demonstrated that the progestational agent, megestrol acetate, has both appetite-enhancing and weight-promoting properties.
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PMID:Management of cancer anorexia/cachexia. 777 79

Like benzodiazepines receptor (BDZR) ligands, 3 alpha-hydroxylated, 5 alpha, or 5 beta pregnane steroids are sedative, anticonvulsant, and anxiolytic. BDZR ligands also modulate the feeding response. Therefore, in this study we have investigated the effects of four 3 alpha-hydroxylated pregnane steroids-Pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one), allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), alphaxalone (3 alpha-hydroxy-5 alpha-pregnan-11,20-dione), and 5 beta-pregnanediol (5 beta-pregnan-3 alpha,20 alpha-diol) on food intake. In non-food deprived male rats, all four steroids increased the consumption of a palatable diet. For pregnanolone (1-10 mg/kg), hyperphagia was found at lower doses than its anxiolytic effect (5-10 mg/kg) as determined using the elevated plus maze test. The presumed steroid antagonists, isopregnanolone (3 beta-hydroxy-5 alpha-pregnan-20-one) (10 mg/kg) and pregnenolone sulfate (2 mg/kg), and the BDZ antagonist, Ro15-1788 (20 mg/kg), did not reverse the hyperphagic effect of pregnanolone. Picrotoxin, a GABAA receptor antagonist, dose dependently and at a subconvulsive dose (1.5 mg/kg), reversed the hyperphagic effect of pregnanolone and alphaxalone, but had no effect on allopregnanolone- and 5 beta-pregnanediol-induced hyperphagia. These results indicate that the hyperphagic effects of pregnanolone and alphaxalone are mediated by the GABAA receptor but not by direct interaction with BDZ receptors. However, allopregnanolone- and 5 beta-pregnanediol-induced hyperphagia may be mediated by other receptor systems. Because some 3 alpha-hydroxylated pregnane steroids are endogenous progesterone metabolites, they may play an important role in appetite control.
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PMID:The hyperphagic effect of 3 alpha-hydroxylated pregnane steroids in male rats. 880 78

The present studies were undertaken to investigate the neuroactive steroidal modulation of feeding behavior and possible involvement of gamma-aminobutyric acid type-A (GABA-A) and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) in food-deprived male mice. Allopregnanolone (0.5-2 mg/kg), a neurosteroid, progesterone (1-10 mg/kg), a neurosteroid precursor, and 4'-chlordiazepam (0.25-1 mg/kg), a specific high affinity MDR agonist, produced a dose-dependent hyperphagic effects. In contrast, neurosteroids pregnenolone sulfate (PS) (1-10 mg/kg) and dehydroepiandrosterone sulfate (DHEAS) (1-10 mg/kg) produced a hypophagic effect, in a dose-dependent manner. The allopregnanolone-, progesterone- and 4'-chlordiazepam-induced hyperphagic effect was blocked by picrotoxin (1 mg/kg), a GABA-A chloride channel antagonist, but not by flumazenil (2 mg/kg), a benzodiazepine (BZD) antagonist. The 4'-chlordiazepam-induced hyperphagic effect was prevented by pretreatment with PK11195 (2 mg/kg), a selective partial MDR antagonist. The hypophagic effect of DHEAS (10 mg/kg) was reversed by dizocilpine (10 microg/kg), an NMDA receptor antagonist, but resistant to muscimol (0.1 mg/kg), a selective GABA-A receptor agonist. In contrast, the PS (10 mg/kg)-induced hypophagic response was resistant to dizocilpine, but sensitive to muscimol (0.1 mg/kg). Both the sulfated neurosteroids PS and DHEAS also reversed the hyperphagic effect of allopregnanolone. In addition, the BZD agonist triazolam (0.05-0.25 mg/kg) also produced a flumazenil- and picrotoxin-sensitive hyperphagic effects, thereby suggesting the changes in feeding behavior by neurosteroids represent GABA-A receptor mediated hyperphagic action. Although the possible antistress or anxiolytic actions of neurosteroids may confound the hyperphagia, behavioral effects observed were specific to food because the mice were adopted to the test environment and diet, and of a possible variation between various neurosteroids in the extent to which antistress or anxiolytic effect produced at hyperphagic doses. The hyperphagic effects of progesterone and 4'-chlordiazepam resembled that of neurosteroid allopregnanolone. Therefore, the effect of progesterone may be imputed to its metabolism to allopregnanolone, while the 4'-chlordiazepam-induced hyperphagic response is related to its MDR-stimulated neurosteroidogenesis and subsequent modulation of GABA-A receptors. The hypophagic response following DHEAS may, at least partly, involve an NMDA receptor mechanism. However, PS-induced hypophagia may be mediated by GABA-A or other receptor systems. These data suggest a pivotal role for GABA-A and mitochondrial DBI receptors in the hyperphagic effects of neurosteroids and reinforces a role for endogenous neurosteroids in regulating feeding behavior. Future studies may lead to the development of neurosteroid-based anorectic/hyperphagic agents for therapeutic use.
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PMID:The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice. 967

In an attempt to elucidate the effect of vanadium compounds on the gene expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally administrated at the dose of 1 mg/kg body weight into streptozotocin-induced diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked lowering of plasma glucose with a significant decrease of food and water intake in these STZ-diabetic rats treated with VOSO4, although the weight gain was unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide concentration, in STZ-diabetic rats was also reduced by this oral treatment of VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the feeding behavior and hypothalamic NPY gene expression. These data suggest that decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery of hyperphagia in diabetic rats lacking insulin.
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PMID:Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in streptozotocin-induced diabetic rats. 1129


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