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Catoire, M., S. Alex, N. Paraskevopulos, F. Mattijsse, I. Evers-van Gogh, G. Schaart, J. Jeppesen, A. Kneppers, M. Mensink, P. Voshol, G. Olivecrona, N. Soon Tan, M. Hesselink, J. Berbée, P.C.N. Rensen, E. Kalkhoven, P. Schrauwen and S. Kersten. 2014. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise. PNAS. 111(11):E1043-E1052.

Number of pages: 10

DOI: 10.1073/pnas.1400889111

Type of document: Journal Article

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More information on authors/freelancers connected to LBI :
Peter Voshol, PhD


Language of document: English

Title in English: Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

Abstract / summary in English:

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.


Keywords in English: Physical activity, energy metabolism , muscle, angiopoietin-like 4 (ANGPTL4), PPAR, plasma triglycerides, Type 2 Diabetes, Metabolic Syndrome, Pre-diabetes
Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise