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Titolo:
Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus
Autore:
Korner, J; Savontaus, E; Chua, SC; Leibel, RL; Wardlaw, SL;
Indirizzi:
Columbia Univ Coll Phys & Surg, Dept Med, Div Endocrinol, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA
Titolo Testata:
JOURNAL OF NEUROENDOCRINOLOGY
fascicolo: 11, volume: 13, anno: 2001,
pagine: 959 - 966
SICI:
0953-8194(200111)13:11<959:LROAAN>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESSENGER-RIBONUCLEIC-ACID; AGOUTI-RELATED PROTEIN; OBESE ZUCKER RATS; NEUROPEPTIDE-Y; GENE-EXPRESSION; ARCUATE NUCLEUS; FOOD-DEPRIVATION; RNA EXPRESSION; BODY-WEIGHT; PROOPIOMELANOCORTIN;
Keywords:
AGRP; NPY; POMC; leptin; obesity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Korner, J Columbia Univ Coll Phys & Surg, Dept Med, Div Endocrinol, 630 W 168th St,Black Bldg,Room 905, New York, NY 10032 USA Columbia Univ Coll Phys & Surg 630 W 168th St,Black Bldg,Room 905 New York NY USA 10032
Citazione:
J. Korner et al., "Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus", J NEUROENDO, 13(11), 2001, pp. 959-966

Abstract

Agouti-related protein (AGRP) is synthesized in the same neurones in the arcuate nucleus as neuropeptide Y (NPY), another potent orexigenic peptide. AGRP antagonizes the action of alpha -melanocyte stimulating hormone, a derivative of pro-opiomelanocortin (POMC) at the hypothalamic MC4 receptor to increase food intake. Although leptin has been shown to regulate Agrp/Npy and Pomc-expressing neurones, there are differences with respect to Agrp regulation in leptin receptor-deficient mice and rats. Unlike the obese leptinreceptor-deficient db/db mouse, which exhibits upregulation of Agrp mRNA expression in the medial basal hypothalamus (MBH) compared to lean controls,the obese leptin receptor-deficient (fa; Koletsky) rat does not exhibit upregulation of Agrp expression. To determine whether this represents a general difference between leptin receptor-deficient mice and rats, neuropeptidegene expression was analysed in the MBH of lean and obese rats segregatingfor a different leptin receptor mutation, Lepr(ia) (Zucker). Fasting in lean rats (+/fa) for 72 h significantly increased Agrp and Npy mRNA expression, and decreased Pomc mRNA expression as detected by a sensitive solution hybridization/S1 nuclease protection assay. Npy mRNA levels were significantly increased in fed obese fa/fa compared to lean rats, and further increased in the obese animals after fasting. In contrast, Agrp mRNA levels did notdiffer between fed lean and fed obese rats, and fasting did not significantly change Agrp levels in obese rats. To determine whether the change in Agrp expression that occurs with food deprivation in lean rats could be prevented by leptin replacement, Sprague-Dawley rats were fasted and infused viasubcutaneous osmotic micropumps for 48 h with either saline or recombinantmouse leptin. Fasting significantly increased Agrp and Npy, and decreased Pomc mRNA levels. Leptin infusion almost completely reversed these changes such that there was no significant difference between the levels in the fasted rats and those that were fed ad libitum. Thus, in fasted lean rats, Agrp and Npy are upregulated in parallel when leptin levels fall and are downregulated by leptin infusion. By contrast, the absence of a functional leptin receptor results in the upregulation of Npy but not Agrp mRNA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 09:55:08