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: Ren Zhang, Abdul B Abou-Samra
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 432 Issue 3 Pg. 401-5 (Mar 15 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23415864 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• ANGPTL3 protein, human
• ANGPTL4 protein, human
• ANGPTL8 protein, human
• Angiopoietin-Like Protein 3
• Angiopoietin-Like Protein 4
• Angiopoietin-Like Protein 8
• Angiopoietin-like Proteins
• Angiopoietins
• Cholesterol, HDL
• Cholesterol, LDL
• Peptide Hormones
• Triglycerides
• Lipoprotein Lipase

Topics

• Adipogenesis
• Angiopoietin-Like Protein 3
• Angiopoietin-Like Protein 4
• Angiopoietin-Like Protein 8
• Angiopoietin-like Proteins
• Angiopoietins (chemistry, metabolism)
• Animals
• Cholesterol, HDL (blood, metabolism)
• Cholesterol, LDL (blood, metabolism)
• Cold Temperature
• Humans
• Lipid Metabolism
• Lipoprotein Lipase (antagonists & inhibitors)
• Metabolic Syndrome (complications, genetics, metabolism)
• Mice
• Peptide Hormones (chemistry, genetics, metabolism)
• Protein Conformation
• Triglycerides (blood, metabolism)