title: Angptl3 regulates lipid metabolism in mice.
abstract: The KK obese mouse is moderately obese and has abnormally high levels of plasma insulin (hyperinsulinemia), glucose (hyperglycemia) and lipids (hyperlipidemia). In one strain (KK/San), we observed abnormally low plasma lipid levels (hypolipidemia). This mutant phenotype is inherited recessively as a mendelian trait. Here we report the mapping of the hypolipidemia (hypl) locus to the middle of chromosome 4 and positional cloning of the autosomal recessive mutation responsible for the hypolipidemia. The hypl locus encodes a unique angiopoietin-like lipoprotein modulator, which we named Allm1. It is identical to angiopoietin-like protein 3, encoded by Angptl3, and has a highly conserved counterpart in humans. Overexpression of Angptl3 or intravenous injection of the purified protein in KK/San mice elicited an increase in circulating plasma lipid levels. This increase was also observed in C57BL/6J normal mice. Taken together, these data suggest that Angptl3 regulates lipid metabolism in animals.
authors.affiliation: Biomedical Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. koishi@shina.sankyo.co.jp
authors.forename: Ryuta
authors.initials: R
authors.lastname: Koishi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ando
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ono
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shimamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yasumo
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Horikoshi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D000595:Amino Acid Sequence; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005808:Genes, Recessive; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype
chemical_list: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D018076:DNA, Complementary; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids