Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (36), p.13163-13168
• Main Authors: Li, Ziru, Xu, Geyang, Qin, Yan, Zhang, Chao, Tang, Hong, Yin, Yue, Xiang, Xinxin, Li, Yin, Zhao, Jing, Mulholland, Michael, Zhang, Weizhen
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; birds of prey; energy metabolism; Fatty Liver - metabolism; Fatty Liver - pathology; Gene Deletion; Gene expression regulation; ghrelin; Ghrelin - pharmacology; ghrelin receptors; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Lipid metabolism; Lipids; Lipogenesis; Lipogenesis - drug effects; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; mammals; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; PPAR gamma - metabolism; Protein Binding - drug effects; Receptors; Receptors, Ghrelin - metabolism; signal transduction; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Triglycerides
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1411571111

Significance The peripheral effect of ghrelin on energy metabolism has been controversial. Our study demonstrates a direct peripheral effect of ghrelin to increase de novo lipogenesis in hepatocytes. Moreover, we define mammalian target of rapamycin (mTOR)-peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathway as the intracellular target of ghrelin in hepatocytes. The effect of ghrelin is mediated by the direct interaction between raptor and PPARγ. Our study identifies a previously unidentified pathway to treat NFALD via targeting hepatic ghrelin receptor/mTOR/PPARγ.