Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Milène Catoire
  • Sheril Alex
  • Nicolas Paraskevopulos
  • Frits Mattijssen
  • Inkie Evers-van Gogh
  • Gert Schaart
  • Jacob Fuglsbjerg Jeppesen
  • Anita Kneppers
  • Marco Mensink
  • Peter J Voshol
  • Gunilla Olivecrona
  • Nguan Soon Tan
  • Matthijs K C Hesselink
  • Jimmy F Berbée
  • Patrick C N Rensen
  • Eric Kalkhoven
  • Patrick Schrauwen
  • Sander Kersten

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.

TidsskriftProceedings of the National Academy of Sciences of the United States of America
Udgave nummer11
Sider (fra-til)E1043-E1052
Antal sider10
StatusUdgivet - 2014

Bibliografisk note

CURIS 2014 NEXS 364

ID: 128655902