title: AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1.
abstract: The aim of this study was to characterize the mechanism by which peripheral nesfatin-1 regulates hepatic lipid metabolism. Continuous peripheral infusion of nesfatin-1 reduced adiposity and plasma levels of triglyceride and cholesterol. In mice fed high fat diet, peripheral nesfatin-1 significantly decreased hepatic steatosis measured by triglyceride content and oil red staining area and diameter. These alterations were associated with a significant reduction in lipogenesis-related transcriptional factors PPARγ and SREBP1, as well as rate-limited enzyme genes such as acaca, fasn, gpam, dgat1 and dgat2. In primary hepatocytes, nesfatin-1 inhibited both basal and oleic acid stimulated triglyceride accumulation, which was accompanied by a decrement in lipogenesis-related genes and an increase in β-oxidation-related genes. In cultured hepatocytes, nesfatin-1 increased levels of AMPK phosphorylation. Inhibition of AMPK by compound C blocked the reduction of triglyceride content elicited by nesfatin-1. Our studies demonstrate that nesfatin-1 attenuates lipid accumulation in hepatocytes by an AMPK-dependent mechanism.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0346, USA. Electronic address: weizhenz@umich.edu.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D002135:Calcium-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007262:Infusions, Intravenous; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D000080866:Nucleobindins; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D014280:Triglycerides; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Hepatocytes; NAFLD; Triglyceride; X/A like cells