title: Emerging roles of Lipasin as a critical lipid regulator.
abstract: Patients with metabolic syndrome are at high risk for developing atherosclerotic cardiovascular diseases and diabetes. In addition to total cholesterol, LDL-C and HDL-C, elevated plasma triglycerides (TG) are increasingly recognized as an independent risk factor for cardiovascular diseases. Recently 3 groups independently reported the identification and characterization of a novel blood lipid regulator, Lipasin/RIFL/ANGPTL8, which here is referred to as Lipasin for its lipoprotein lipase inhibition effect and for being a circulating factor denoted by 'in'. Being highly enriched in the liver, Lipasin is a hepatocyte-derived circulating factor that regulates plasma TG levels. Lipasin is nutritionally regulated, as its mRNA levels in liver and fat as well as its protein level in serum are reduced by fasting. Mice deficient for Lipasin have lower serum TG levels; conversely, its adenovirus-mediated overexpression increases serum TG levels, in part, through promoting ANGPTL3 cleavage, releasing its N-terminal domain that inhibits lipoprotein lipase. Lipasin sequence variations are associated with LDL-C and HDL-C concentrations in humans. Being lipogenic, Lipasin is highly induced during adipogenesis. Levels of Lipasin and ANGPTL4 show opposite changes in response to fasting or cold environment. Lipasin, a novel but atypical ANGPTL family member, is emerging as a critical lipid regulator and a potential drug target.
authors: Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA. rzhang@med.wayne.edu
authors: Ren
authors: R
authors: Zhang
authors: Abdul B
authors: AB
authors: Abou-Samra
mesh_terms: D050156:Adipogenesis; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003080:Cold Temperature; D006801:Humans; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051379:Mice; D036361:Peptide Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: C479896:ANGPTL3 protein, human; C474772:ANGPTL4 protein, human; C576683:ANGPTL8 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D036361:Peptide Hormones; D014280:Triglycerides; D008071:Lipoprotein Lipase