title: Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family.
abstract: Hyperlipidemia is a major contributor to cardiovascular diseases. Members of the angiopoietin-like protein family (ANGPTLs) are important determinants of blood lipid levels. Lipasin, a newly identified gene that regulates serum triglycerides, is homologous to ANGPTL3's N-terminal domain, which is sufficient and necessary for blood lipid regulation. Brown fat is critical in mediating energy homeostasis. Thermogenesis is the primary function of brown fat, in which Lipasin and some ANGPTLs are abundant; it is unknown, however, whether these genes are thermoregulated. We therefore comprehensively examined the thermoregulation of Lipasin and ANGPTLs in brown fat. Here we show that Lipasin is a novel but atypical member of the ANGPTL family because it is within the same branch as ANGPTL3 and 4 by phylogenetic analysis. The mRNA levels of Lipasin are dramatically increased in the cold environment (4 °C for 4 h) whereas those of ANGPTL4 and ANGPTL2 are suppressed. Fasting dramatically suppresses Lipasin but increases ANGPTL4. High-fat diet treatment increases Lipasin, but reduces ANGPTL2. The distinct transcriptional regulations of Lipasin, ANGPTL2 and ANGPTL4 in brown fat in response to cold exposure and nutritional stimulation suggest distinct physiological roles for ANGPTL family members in mediating thermogenesis and energy homeostasis.
authors.affiliation: Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit 48201, USA.
authors.forename: Zhiyao
authors.initials: Z
authors.lastname: Fu
authors.forename: Fayi
authors.initials: F
authors.lastname: Yao
authors.forename: Abdul B
authors.initials: AB
authors.lastname: Abou-Samra
authors.forename: Ren
authors.initials: R
authors.lastname: Zhang
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001833:Body Temperature Regulation; D003080:Cold Temperature; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036361:Peptide Hormones / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary
chemical_list: C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D036361:Peptide Hormones