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Publication : Hepatic ANGPTL3 regulates adipose tissue energy homeostasis.

First Author  Wang Y Year  2015
Journal  Proc Natl Acad Sci U S A Volume  112
Issue  37 Pages  11630-5
PubMed ID  26305978 Mgi Jnum  J:226803
Mgi Id  MGI:5698587 Doi  10.1073/pnas.1515374112
Citation  Wang Y, et al. (2015) Hepatic ANGPTL3 regulates adipose tissue energy homeostasis. Proc Natl Acad Sci U S A 112(37):11630-5
abstractText  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.
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