Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels.
The metabolic syndrome, a common disorder including glucose intolerance and dyslipidemia, poses a major public health issue. Patients with high blood lipids, such as triglycerides, are at high risk in developing atherosclerotic cardiovascular diseases. To identify genes involved in metabolism, we performed RNA-seq experiments on the liver and fat in mice treated with a high-fat diet or fasting, and identified Gm6484 (named Lipasin) as a novel nutritionally regulated gene. Human LIPASIN is liver specific, while the mouse one is enriched in the liver and fat, including both brown and white adipose tissues. Obesity increases liver Lipasin, whereas fasting reduces its expression in fat. ANGPTL3 (Angiopoietin-like 3) and ANGPTL4 are critical regulators of blood lipids. LIPASIN shares homology with ANGPTL3's N-terminal domain that is needed for lipid regulation, and with ANGPTL4's N-terminal segment that mediates lipoprotein lipase (LPL) binding. Lipasin overexpression by adenoviruses in mice increases serum triglyceride levels, and a recombinant Lipasin inhibits LPL activity. Therefore, a potential mechanism for Lipasin-mediated triglyceride elevation is through reduced triglyceride clearance by LPL inhibition. Lipasin is thus a novel nutritionally-regulated liver-enriched factor that plays a role in lipid metabolism.
Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA. rzhang@med.wayne.edu
Ren
R
Zhang
D000595:Amino Acid Sequence; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017124:Conserved Sequence; D050171:Dyslipidemias / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009747:Nutritional Physiological Phenomena; D036361:Peptide Hormones; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood*
C576683:ANGPTL8 protein, human; C000595899:ANGPTL8 protein, mouse; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; C407088:Angptl4 protein, mouse; D036361:Peptide Hormones; D011506:Proteins; D014280:Triglycerides