title: Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling.
abstract: Irisin, a myokine released during exercise, promotes browning of subcutaneous adipose tissue and regulates energy homeostasis. Although exercise constantly reduces blood cholesterol, whether irisin is involved in the regulation of cholesterol remains largely unknown. In the present study, subcutaneous infusion of irisin for 2weeks induced a reduction in plasma and hepatic cholesterol in high fat diet-induced obese (DIO) mice. These alterations were associated with an activation of 5' AMP-activated protein kinase (AMPK) and inhibition of sterol regulatory element-binding transcription factor 2 (SREBP2) transcription and nuclear translocation. In primary hepatocytes from either lean or DIO mice, irisin significantly decreased cholesterol content via sequential activation of AMPK and inhibition of SREBP2. Suppression of AMPK by compound C or AMPKα1 siRNA blocked irisin-induced alterations in cholesterol contents and SREBP2. In conclusion, irisin could suppress hepatic cholesterol production via a mechanism dependent of AMPK and SREBP2 signaling. These findings suggest that irisin is a promising therapeutic target for treatment of hypercholesterolemia.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China. Electronic address: tangyunlian626@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China. Electronic address: yyyrrrlll@126.com.
authors.forename: Ruili
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China. Electronic address: from_jessica@163.com.
authors.forename: Shiying
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China. Electronic address: tafcalgen@163.com.
authors.forename: Bahetiyaer
authors.initials: B
authors.lastname: Huwatibieke
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0346, USA. Electronic address: liziru@umich.edu.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, 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 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000737:chemistry; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Cholesterol; Irisin; Liver; SREBP2