Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

Yan Wang, Markey C. McNutt, Serena Banfi, Michael G. Levin, William L. Holland, Viktoria Gusarova, Jesper Gromada, Jonathan C. Cohen, Helen H. Hobbs

Research output: Contribution to journalArticle

45 Scopus citations

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 inWAT, 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.

Original languageEnglish (US)
Pages (from-to)11630-11635
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number37
DOIs
StatePublished - Sep 15 2015

Keywords

  • Angiopoietin
  • Glucose
  • Insulin
  • Lipoprotein lipase
  • Triglyceride

ASJC Scopus subject areas

  • General

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