TM6SF2: A novel target for plasma lipid regulation

• Published in: Atherosclerosis 2018-01, Vol.268, p.170-176
• Main Authors: Li, Ting-Ting, Li, Tao-Hua, Peng, Juan, He, Bei, Liu, Lu-Shan, Wei, Dang-Heng, Jiang, Zhi-Sheng, Zheng, Xi-Long, Tang, Zhi-Han
• Format: Article
• Language: English
• Subjects: Animals; Anticholesteremic Agents - therapeutic use; Biomarkers - blood; Cardiovascular disease; Cholesterol - blood; Dyslipidemias - blood; Dyslipidemias - diagnosis; Dyslipidemias - drug therapy; Dyslipidemias - genetics; Humans; Intestinal Absorption - drug effects; Liver - drug effects; Liver - metabolism; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Transgenic; Plasma lipids; Transmembrane 6 superfamily 2
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2017.11.033

Transmembrane 6 superfamily 2 (TM6SF2), a gene identified at the locus 19p12, has been recognized to regulate plasma lipids. Here, we provide an overview of the roles of TM6SF2 as a novel target for plasma lipid regulation. We first review the association of TM6SF2 variant with plasma lipid traits, cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Then, we present an overview about the in vivo validation of TM6SF2 as a regulator of plasma lipid levels using mice, with overexpression or knockdown/knockout of TM6SF2. Thereafter, we discuss the mechanisms underlying TM6SF2 regulation of lipid metabolism involving intestinal cholesterol absorption and hepatic cholesterol biosynthesis and transport. In conclusion, increasing evidence suggests that TM6SF2 may be a major regulator of plasma lipid levels and become a therapeutic target in cardiovascular disease. •TM6SF2 E167K variant is associated with plasma lipid traits, CVD and NAFLD.•TM6SF2 can regulate plasma lipid levels.•TM6SF2 may become a therapeutic target in lipid disorder-associated CVD.