Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise
Gogh, Inkie Evers-van
Voshol, Peter J
Tan, Nguan Soon
Hesselink, Matthijs K C
Berbée, Jimmy F
Rensen, Patrick C N
Date of Issue2014
School of Biological Sciences
Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise encodes angiopoietin-like 4 (ANGPTL4), an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. Using a combination of human, animal, and in vitro data, we show that induction of ANGPTL4 in nonexercising muscle is mediated by elevated plasma free fatty acids via peroxisome proliferator-activated receptor-δ, presumably leading to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles. Our data suggest that nonexercising muscle and the local regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing lipid homeostasis during exercise.
DRNTU::Science::Biological sciences::Human anatomy and physiology
Proceedings of the National Academy of Sciences of the United States of America
© 2014 The Author(s). This paper was published in Proceedings of the National Academy of Sciences of the United States of America and is made available as an electronic reprint (preprint) with permission of the Author(s). The paper can be found at the following official DOI: http://dx.doi.org/10.1073/pnas.1400889111. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.