TY - JOUR
T1 - Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling
AU - Stevanovic, Darko
AU - Trajkovic, Vladimir
AU - Müller-Lühlhoff, Sabrina
AU - Brandt, Elisabeth
AU - Abplanalp, William
AU - Bumke-Vogt, Christiane
AU - Liehl, Beate
AU - Wiedmer, Petra
AU - Janjetovic, Kristina
AU - Starcevic, Vesna
AU - Pfeiffer, Andreas F.H.
AU - Al-Hasani, Hadi
AU - Tschöp, Matthias H.
AU - Castañeda, Tamara R.
N1 - Funding Information:
We wish to thank Angelika Horrighs for excellent technical and scientific assistance. The study was supported by a DAAD fellowship to D. Stevanovic and by the Ministry of Science and Technological Development of the Republic of Serbia (Grant 41025) and a Deutsche Diabetes Gesellschaft (DDG) award to T.R. Castañeda.
PY - 2013/12/5
Y1 - 2013/12/5
N2 - 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.
AB - 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.
KW - Body weight
KW - Central nervous system
KW - Food intake
KW - Ghrelin
KW - Insulin
KW - MTORC1/S6K
UR - http://www.scopus.com/inward/record.url?scp=84884231872&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2013.08.009
DO - 10.1016/j.mce.2013.08.009
M3 - Article
C2 - 23994018
AN - SCOPUS:84884231872
SN - 0303-7207
VL - 381
SP - 280
EP - 290
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -