title: Hepatic ANGPTL3 regulates adipose tissue energy homeostasis.
abstract: Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3(-/-) mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3(-/-) animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3(-/-) mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.
authors: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors: Yan
authors: Y
authors: Wang
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors: Markey C
authors: MC
authors: McNutt
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors: Serena
authors: S
authors: Banfi
authors: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors: Michael G
authors: MG
authors: Levin
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors: William L
authors: WL
authors: Holland
authors: Regeneron Pharmaceuticals, Tarrytown, NY 10591.
authors: Viktoria
authors: V
authors: Gusarova
authors: Regeneron Pharmaceuticals, Tarrytown, NY 10591.
authors: Jesper
authors: J
authors: Gromada
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; jonathan.cohen@utsouthwestern.edu helen.hobbs@utsouthwestern.edu.
authors: Jonathan C
authors: JC
authors: Cohen
authors: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; jonathan.cohen@utsouthwestern.edu helen.hobbs@utsouthwestern.edu.
authors: Helen H
authors: HH
authors: Hobbs
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D000242:Cyclic AMP / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006728:Hormones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D001786:Blood Glucose; D005227:Fatty Acids; D006728:Hormones; D007328:Insulin; D014280:Triglycerides; D000242:Cyclic AMP; D008071:Lipoprotein Lipase
keywords: angiopoietin; glucose; insulin; lipoprotein lipase; triglyceride