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

Abstract

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.

• Authors: Darko Stevanovic, Vladimir Trajkovic, Sabrina Müller-Lühlhoff, Elisabeth Brandt, William Abplanalp, Christiane Bumke-Vogt, Beate Liehl, Petra Wiedmer, Kristina Janjetovic, Vesna Starcevic, Andreas F H Pfeiffer, Hadi Al-Hasani, Matthias H Tschöp, Tamara R Castañeda
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 381 Issue 1-2 Pg. 280-90 (Dec 05 2013) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 23994018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Ghrelin
• Insulin
• Ion Channels
• Mitochondrial Proteins
• Multiprotein Complexes
• Uncoupling Protein 1
• mTOR protein, rat
• Mechanistic Target of Rapamycin Complex 1
• Ribosomal Protein S6 Kinases
• Rps6kb1 protein, rat
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Adipose Tissue, Brown (physiology)
• Adiposity (physiology)
• Animals
• Cell Line
• Energy Intake
• Ghrelin (physiology)
• Insulin (blood)
• Ion Channels (metabolism)
• Male
• Mechanistic Target of Rapamycin Complex 1
• Mice
• Mice, Knockout
• Mitochondrial Proteins (metabolism)
• Multiprotein Complexes (antagonists & inhibitors, metabolism)
• Rats
• Rats, Wistar
• Ribosomal Protein S6 Kinases (metabolism)
• Sirolimus (pharmacology)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Uncoupling Protein 1