Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

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

doi:10.1073/pnas.1400889111

Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

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

The August Krogh Section for Molecular Physiology

73 Citations (Scopus)

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.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	11
Pages (from-to)	E1043-E1052
Number of pages	10
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.1400889111
Publication status	Published - 18 Mar 2014

Keywords

Adult
Angiopoietins
Exercise
Fatty Acids
Fluorescent Antibody Technique
Homeostasis
Humans
Lipid Metabolism
Male
Microarray Analysis
Middle Aged
Muscle, Skeletal

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Catoire, M., Alex, S., Paraskevopulos, N., Mattijssen, F., Evers-van Gogh, I., Schaart, G., Jeppesen, J. F., Kneppers, A., Mensink, M., Voshol, P. J., Olivecrona, G., Tan, N. S., Hesselink, M. K. C., Berbée, J. F., Rensen, P. C. N., Kalkhoven, E., Schrauwen, P., & Kersten, S. (2014). Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise. Proceedings of the National Academy of Sciences of the United States of America, 111(11), E1043-E1052. https://doi.org/10.1073/pnas.1400889111

Catoire, M, Alex, S, Paraskevopulos, N, Mattijssen, F, Evers-van Gogh, I, Schaart, G, Jeppesen, JF, Kneppers, A, Mensink, M, Voshol, PJ, Olivecrona, G, Tan, NS, Hesselink, MKC, Berbée, JF, Rensen, PCN, Kalkhoven, E, Schrauwen, P & Kersten, S 2014, 'Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 11, pp. E1043-E1052. https://doi.org/10.1073/pnas.1400889111

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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.",

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AU - Catoire, Milène

AU - Alex, Sheril

AU - Paraskevopulos, Nicolas

AU - Mattijssen, Frits

AU - Evers-van Gogh, Inkie

AU - Schaart, Gert

AU - Jeppesen, Jacob Fuglsbjerg

AU - Kneppers, Anita

AU - Mensink, Marco

AU - Voshol, Peter J

AU - Olivecrona, Gunilla

AU - Tan, Nguan Soon

AU - Hesselink, Matthijs K C

AU - Berbée, Jimmy F

AU - Rensen, Patrick C N

AU - Kalkhoven, Eric

AU - Schrauwen, Patrick

AU - Kersten, Sander

N1 - CURIS 2014 NEXS 364

PY - 2014/3/18

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N2 - 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.

AB - 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.

KW - Adult

KW - Angiopoietins

KW - Exercise

KW - Fatty Acids

KW - Fluorescent Antibody Technique

KW - Homeostasis

KW - Humans

KW - Lipid Metabolism

KW - Male

KW - Microarray Analysis

KW - Middle Aged

KW - Muscle, Skeletal

U2 - 10.1073/pnas.1400889111

DO - 10.1073/pnas.1400889111

M3 - Journal article

C2 - 24591600

SN - 0027-8424

VL - 111

SP - E1043-E1052

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 11

ER -

Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

Abstract

Keywords

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