Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling
2013
Authors:
Stevanović, DarkoTrajković, Vladimir
Müller-Lühlhoff, Sabrina
Brandt, Elisabeth
Abplanalp, William
Bumke-Vogt, Christiane
Liehl, Beate
Wiedmer, Petra
Janjetović, Kristina
Starčević, Vesna
Pfeiffer, Andreas F.H.
Al-Hasani, Hadi
Tschöp, Matthias H.
Castañeda, Tamara R.
Document Type:
Article (Published version)
,
© 2013 Elsevier Ireland Ltd.
Metadata
Show full item recordAbstract:
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.
Keywords:
Ghrelin; Central nervous system; mTORC1/S6K; Food intake; Insulin; Body weightSource:
Molecular and Cellular Endocrinology, 2013, 381, 1-2, 280-290Funding / projects:
- DAAD fellowship dodeljen Darku Stevanovicu
- DDG nagrada dodeljena Tamari R. Castaneda
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
DOI: 10.1016/j.mce.2013.08.009
ISSN: 0303-7207
PubMed: 23994018