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Stevanovic, D.* ; Trajkovic, V.* ; Müller-Lühlhoff, S.* ; Brandt, E.* ; Abplanalp, W.* ; Bumke-Vogt, C.* ; Liehl, B.* ; Wiedmer, P.* ; Janjetovic, K.* ; Starcevic, V.* ; Pfeiffer, A.F.* ; Al-Hasani, H.* ; Tschöp, M.H. ; Castañeda, T.R.*

Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling.

Mol. Cell. Endocrinol. 381, 280-290 (2013)
Open Access Green as soon as Postprint is submitted to ZB.
Signaling through the mammalian target of rapamycin complex 1 (mTORC1) and its effectors the S6-kinases (S6K) in the hypothalamus is thought to be involved in nutrient sensing and control of food intake. Given the anatomical proximity of this pathway to circuits for the hormone ghrelin, we investigated the potential role of the mTORC1/S6K pathway in mediating the metabolic effects of ghrelin. We found that ghrelin promoted phosphorylation of S6K1 in the mouse hypothalamic cell line N-41 and in the rat hypothalamus after intracerebroventricular administration. Rapamycin, an inhibitor of mTORC1, suppressed ghrelin-induced phosphorylation of hypothalamic S6K1 and increased food intake and insulin in rats. Chronic peripheral administration of ghrelin induced a significant increase in body weight, fat mass and food efficiency in wild-type and S6K2-knockout but not in S6K1-knockout mice. We therefore propose that ghrelin-induced hyperphagia, adiposity and insulin secretion are controlled by a central nervous system involving the mTORC1/S6K1 pathway.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Body weight; Central nervous system; Food intake; Ghrelin; Insulin; MTORC1/S6K; Activated Protein-kinase ; Agouti-related Protein ; Diet-induced Obesity ; Mammalian Target ; S6 Kinase ; Orexigenic Action ; Neuropeptide-y ; Rats ; Ampk ; Metabolism
ISSN (print) / ISBN 0303-7207
e-ISSN 1872-8057
Quellenangaben Volume: 381, Issue: 1-2, Pages: 280-290 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Shannon
Reviewing status Peer reviewed