Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes.
Our previous work identified a genetic mutation in the gene encoding angiopoietin-like protein 3 (Angptl3) in KK/Snk mice (previously KK/San), a mutant strain of KK obese mice. KK/Snk had significantly lower plasma triglyceride and free fatty acid (FFA) than KK mice. Human ANGPTL3 treatment increased both plasma triglyceride and FFA. ANGPTL3 inhibited the activity of lipoprotein lipase, which accounted for the increase of plasma triglyceride. The mechanism how ANGPTL3 affects plasma FFA has not been known. The current study reveals that ANGPTL3 targets on adipose cells and induces lipolysis. Both plasma FFA and glycerol decreased in KK/Snk and increased by the treatment of human ANGPTL3. Specific bindings of ANGPTL3 to adipose cells were shown using fluorescence-labeled protein visually and 125I-labeled protein by the binding analysis. Furthermore, ANGPTL3 activated the lipolysis to stimulate the release of FFA and glycerol from adipocytes. We conclude that ANGPTL3 is a liver-derived lipolytic factor targeting on adipocyte.
Shimamura
Mitsuru
M
Department of Medicine and Pathology, Graduate School of Frontier Bioscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
Matsuda
Morihiro
M
Kobayashi
Sachiko
S
Ando
Yosuke
Y
Ono
Mitsuru
M
Koishi
Ryuta
R
Furukawa
Hidehiko
H
Makishima
Makoto
M
Shimomura
Iichiro
I
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005456:Fluorescent Dyes / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D005230:Fatty Acids, Nonesterified; D005456:Fluorescent Dyes; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005990:Glycerol