Angptl3 regulates lipid metabolism in mice.
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.
Koishi
Ryuta
R
Biomedical Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. koishi@shina.sankyo.co.jp
Ando
Yosuke
Y
Ono
Mitsuru
M
Shimamura
Mitsuru
M
Yasumo
Hiroaki
H
Fujiwara
Toshihiko
T
Horikoshi
Hiroyoshi
H
Furukawa
Hidehiko
H
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
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