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Titolo:
Long-term administration of MC4 receptor antagonist HS014 causes hyperphagia and obesity in rats
Autore:
Kask, A; Pahkla, R; Irs, A; Rago, L; Wikberg, JES; Schioth, HB;
Indirizzi:
Tartu State Univ, Dept Pharmacol, EE-2400 Tartu, Estonia Tartu State UnivTartu Estonia EE-2400 Pharmacol, EE-2400 Tartu, Estonia Uppsala Univ, BMC, Dept Pharmaceut Pharmacol, S-75124 Uppsala, Sweden Uppsala Univ Uppsala Sweden S-75124 t Pharmacol, S-75124 Uppsala, Sweden
Titolo Testata:
NEUROREPORT
fascicolo: 4, volume: 10, anno: 1999,
pagine: 707 - 711
SICI:
0959-4965(19990317)10:4<707:LAOMRA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPEPTIDE-Y; FOOD-INTAKE; IN-VIVO; LEPTIN; EXPRESSION; MUTATIONS; DISCOVERY; FRAGMENT; NUCLEUS;
Keywords:
food intake; HS014; leptin resistance; MC4; antagonist; melanocortin (MC) receptor subtypes; obesity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Kask, A Tartu State Univ, Dept Pharmacol, Ulikooli 18, EE-2400 Tartu, Estonia Tartu State Univ Ulikooli 18 Tartu Estonia EE-2400 Tartu, Estonia
Citazione:
A. Kask et al., "Long-term administration of MC4 receptor antagonist HS014 causes hyperphagia and obesity in rats", NEUROREPORT, 10(4), 1999, pp. 707-711

Abstract

IN this study we investigated the long term effects of a potent and selective melanocortin 4 (MC4) receptor antagonist (HS014) on food intake, body weight, body composition and blood glucose levels in adult rats. HS014 was injected i.c.v. either by twice-daily injections (2 x 1 nmol) for 6 days or administered by continuous infusion with osmotic minipumps (0.16 nmol/h) for 2 weeks. The results show a considerable increase in food intake and bodyweight after both of the treatments without any signs of tachyphylaxis. After 2 weeks of treatment with osmotic pumps, the HS014-treated rats (average weight 425 g) had 20% higher body weight than the controls rats (average 360 g). When i.c.v. injections were terminated, the body weight of the twice-daily HS014-trrated rats returned to the levels of control group, whereasthe rats treated with continuous infusion of HS014 remained hyperphagic and still gained weight. Blood glucose levels in the rats treated with HIS014infusion were significantly increased. Analysis of body composition in HS014-infused rats indicated that body weight was increased due to fat deposits. These data show for the first time that chronic administration of exogenous MC4 receptor antagonist causes hyperphagia and severe obesity in rats. These data also indicate that the melanocortic control of food intake is very robust and suggest that changes induced by such treatment overcome negative feedback signals. NeuroReport 10: 711-711 (C) 1999 Lippincott Williams & Wilkins.

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Documento generato il 15/07/20 alle ore 07:21:29