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Angiopoietin-like 4 directs uptake of dietary fat away from adipose during fasting
Journal article   Open access   Peer reviewed

Angiopoietin-like 4 directs uptake of dietary fat away from adipose during fasting

Emily M Cushing, Xun Chi, Kelli L Sylvers, Shwetha K Shetty, Matthew J Potthoff and Brandon S.J Davies
Molecular metabolism (Germany), Vol.6(8), pp.809-818
08/2017
DOI: 10.1016/j.molmet.2017.06.007
PMCID: PMC5518724
PMID: 28752045
url
https://doi.org/10.1016/j.molmet.2017.06.007View
Published (Version of record) Open Access

Abstract

Angiopoietin-like 4 (ANGPTL4) is a fasting-induced inhibitor of lipoprotein lipase (LPL) and a regulator of plasma triglyceride metabolism. Here, we examined the kinetics of Angptl4 induction and tested the hypothesis that ANGPTL4 functions physiologically to reduce triglyceride delivery to adipose tissue during nutrient deprivation. Gene expression, LPL activity, and triglyceride uptake were examined in fasted and fed wild-type and Angptl4−/− mice. Angptl4 was strongly induced early in fasting, and this induction was suppressed in mice with access to food during the light cycle. Fasted Angptl4−/− mice manifested increased LPL activity and triglyceride uptake in adipose tissue compared to wild-type mice. Angptl4 is induced early in fasting to divert uptake of fatty acids and triglycerides away from adipose tissues. •Angptl4 is induced within the first few hours of fasting.•Angptl4 expression is driven by fasting rather than circadian rhythms.•Fasted Angptl4−/− mice have increased triglyceride uptake in adipose tissue.•Angptl4−/− mice also have increased LPL activity specifically in adipose tissue.•Data support a model where ANGPTL4 acts locally in adipose during fasting.
Lipase inhibition Lipoprotein metabolism Lipolysis Plasma triglycerides

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