title: Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise.
abstract: 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.
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6700 EV, Wageningen, The Netherlands.
authors.forename: Milène
authors.initials: M
authors.lastname: Catoire
authors.forename: Sheril
authors.initials: S
authors.lastname: Alex
authors.forename: Nicolas
authors.initials: N
authors.lastname: Paraskevopulos
authors.forename: Frits
authors.initials: F
authors.lastname: Mattijssen
authors.forename: Inkie
authors.initials: I
authors.lastname: Evers-van Gogh
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Jacob
authors.initials: J
authors.lastname: Jeppesen
authors.forename: Anita
authors.initials: A
authors.lastname: Kneppers
authors.forename: Marco
authors.initials: M
authors.lastname: Mensink
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Nguan Soon
authors.initials: NS
authors.lastname: Tan
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: Jimmy F
authors.initials: JF
authors.lastname: Berbée
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Eric
authors.initials: E
authors.lastname: Kalkhoven
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
mesh_terms: D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D005227:Fatty Acids