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Titolo:
Downregulation of fasting-induced cAMP response element-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus
Autore:
Shimizu-Albergine, M; Ippolito, DL; Beavo, JA;
Indirizzi:
Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 ept Pharmacol, Seattle, WA 98195 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 4, volume: 21, anno: 2001,
pagine: 1238 - 1246
SICI:
0270-6474(20010215)21:4<1238:DOFCRE>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROOPIOMELANOCORTIN MESSENGER-RNA; AGOUTI-RELATED PROTEIN; FOOD-INTAKE; OB/OB MICE; ENERGY HOMEOSTASIS; RAT HYPOTHALAMUS; BINDING PROTEIN; PHORBOL ESTER; OBESE GENE; CYCLIC-AMP;
Keywords:
arcuate nucleus; cAMP; CRE; CREB; leptin; NPY; PKA; PDE inhibitor; POMC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Beavo, JA Univ Washington, Sch Med, Dept Pharmacol, Box 357280, Seattle, WA 98195 USA Univ Washington Box 357280 Seattle WA USA 98195 le, WA 98195 USA
Citazione:
M. Shimizu-Albergine et al., "Downregulation of fasting-induced cAMP response element-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus", J NEUROSC, 21(4), 2001, pp. 1238-1246

Abstract

States of increased metabolic demand such as fasting modulate hypothalamicneuropeptide gene expression and decrease circulating leptin levels. This study tested the hypotheses that fasting stimulates gene induction mediatedby cAMP response element (CRE)-dependent increases in gene transcription and that fasting-induced decreases in leptin can regulate this CRE-mediated gene induction. Using C57BL/6J mice transgenic for a CRE-lacZ construct, animmunocytochemical study showed that fasting activated reporter gene expression in the hypothalamic arcuate nucleus (Arc) in a small subset of neurons and increased phosphorylation of CRE binding protein. The increase of beta -galactosidase expression caused by fasting was inhibited by a protein kinase A inhibitor, Rp-8-Br-cAMPS, when the compound was microinjected into the medial basal hypothalamus, and enhanced by intraperitoneal injection of selective phosphodiesterase inhibitors. In situ hybridization studies showed that neuropeptide Y (NPY) mRNA levels increased in the Arc during fasting, whereas proopiomelanocortin (POMC) mRNA levels decreased. Double labelingof mRNA and beta -galactosidase immunoreactivity in the fasted brain indicated that the subpopulation of the neurons expressing beta -galactosidase all produced NPY but not POMC. To study the possible involvement of decreased circulating leptin during starvation on CRE-mediated gene induction, leptin was administered intraperitoneally to fasted mice. Leptin significantly attenuated both b-galactosidase expression and NPY gene expression stimulated by fasting, suggesting that leptin inhibits fasting-stimulated NPY gene expression at least in part through downregulation of CRE-mediated gene induction in the Arc. Leptin-induced modification of CRE-mediated gene induction in the Arc may play an essential role in the central regulation of feeding behavior and energy expenditure.

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Documento generato il 22/01/20 alle ore 13:09:18