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)

Treatment of male rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a dose-dependent decrease in body weight, feed intake, resting and total oxygen consumption, and spontaneous motor activity. In animals treated with a nonlethal dose (5 or 15 micrograms/kg), feed intake and oxygen consumption recover within 3 weeks post-treatment to levels appropriate for the reduced weight of the animals. Rats treated with a lethal dose (50 micrograms/kg) lose weight continuously after treatment and typically die at a body weight approximately half that of age-matched, control rats. The similar dose and time dependencies for reduction of feed intake and weight suggest that hypophagia is the major factor responsible for weight loss in TCDD-treated rats. To determine if this hypophagia is a primary or secondary effect of TCDD treatment, rats whose body weights were reduced by food restriction prior to treatment (25 micrograms/kg) were studied. When allowed to feed ad libitum immediately after treatment, these animals exhibited relative hyperphagia and weight gain demonstrating that TCDD did not impair their capacity to feed. This finding suggests that the primary effect of TCDD is not on a system that controls feed intake, but rather on one that regulates body weight. It is proposed, as a heuristic model of the wasting syndrome, that TCDD treatment lowers a "set point" for regulated body weight in the rat in a dose-dependent fashion and that hypophagia serves, as a secondary response, to reduce the animal's weight to the lower regulation level determined by the dose administered.
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PMID:Characterization of the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. 671 May 31

Cachexia is a clinical wasting syndrome that occurs in multiple disease states, and is associated with anorexia and a progressive loss of body fat and lean mass. The development of new therapeutics for this disorder is needed due to poor efficacy and multiple side effects of current therapies. The pivotal role played by the central melanocortin system in regulating body weight has made this an attractive target for novel cachexia therapies. The mixed melanocortin receptor antagonist AgRP is an endogenous peptide that induces hyperphagia. Here, we used AgRP(83-132) to investigate the ability of melanocortin antagonism to protect against clinical features of cachexia in two distinct animal models. In an acute model, food intake and body weight gain were reduced in mice exposed to radiation (300 RAD), and delivery of AgRP(83-132) into the lateral cerebral ventricle prevented these effects. In a chronic tumor cachexia model, adult mice were injected subcutaneously with a cell line derived from murine colon-26 adenocarcinoma. Typical of cachexia, tumor-bearing mice progressively reduced body weight and food intake, and gained significantly less muscle mass than controls. Administration of AgRP(83-132) into the lateral ventricles significantly increased body weight and food intake, and changes in muscle mass were similar to the tumor-free control mice. These findings support the idea that antagonism of the central melanocortin system can reduce the negative impact of cachexia and radiation therapy.
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PMID:Central infusion of the melanocortin receptor antagonist agouti-related peptide (AgRP(83-132)) prevents cachexia-related symptoms induced by radiation and colon-26 tumors in mice. 1720 51