Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise
Open accessAbstract
Significance: Physical exercise causes profound changes in energy metabolism in humans. In this study we show that resting skeletal muscle has a crucial role in the metabolic response to acute exercise. During endurance exercise, selective induction of the protein angiopoietin-like 4 (ANGPTL4) in nonexercising muscle reduces local fatty acid uptake, presumably to prevent fat overload, while directing fatty acids to the active skeletal muscle as fuel. Our data thus suggest that nonexercising muscle has a key role in governing lipid homeostasis during exercise.
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ANGPTL4 is upregulated by SkM after aerobic or resistance exercise.
“Although it is upregulated by SkM after aerobic or resistance exercise [171,172,196], surprisingly, an even greater degree of ANGPTL4 mRNA expression was found in the portion of SkM that remained inactive during the bout of exercise compared with the active SkM [172,196], representing a mechanism to redistribute FFA delivery from unexercised to exercised SkM.”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [172]
The Results (page unavailable) report ANGPTL4 induction in skeletal muscle after acute one-legged cycling, especially in the nonexercising leg. This supports upregulation after aerobic exercise, but the paper does not establish upregulation after resistance exercise. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAn even greater degree of ANGPTL4 mRNA expression was found in the portion of SkM that remained inactive during the bout of exercise compared with the active SkM.
“Although it is upregulated by SkM after aerobic or resistance exercise [171,172,196], surprisingly, an even greater degree of ANGPTL4 mRNA expression was found in the portion of SkM that remained inactive during the bout of exercise compared with the active SkM [172,196], representing a mechanism to redistribute FFA delivery from unexercised to exercised SkM.”
Acute exercise in humans releases molecules such as GDF15 and IL-6 that affect lipolysis, in addition to adrenaline.
“acute exercise in humans also releases additional molecules79, such as growth and differentiation factor 15 (GDF15)80 and IL-6 (REF.81), which also affect lipolysis”
From Exerkines in health, resilience and disease (2022) · cites this paper as [79]
Liver-derived exerkines affect glucose and/or lipid metabolism, WAT browning, lipolysis and cellular homeostasis.
“These exerkines affect glucose and/or lipid metabolism (for example, angiopoietin-like protein 4 in humans and animal models39,79), browning of WAT (FGF21 in a mouse model106), lipolysis (FGF21 in humans and a mouse model77) and the maintenance of cellular homeostasis (heat shock protein 72 in humans107).”
From Exerkines in health, resilience and disease (2022) · cites this paper as [79]
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- Authors
- Catoire, M., Alex, S., Paraskevopulos, N., Mattijssen, F., Evers-van Gogh, I., Schaart, G., Jeppesen, J., 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.
- Affiliations
- Wageningen University & Research (NL)
- Department of Metabolic Diseases, University Medical Centre Utrecht, 3584 EA, Utrecht, The Netherlands;
- Departments of cHuman Movement Sciences and
- University of Copenhagen (DK)
- University of Cambridge (GB)
- Umeå University (SE)
- Nanyang Technological University (SG)
- Leiden University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Maastricht University Medical Centre (NL)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-03-03
- Volume
- 111
- Issue
- 11
- Pages
- E1043-52
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3964070
- OpenAlex
- W2078778450
- Cited by
- 150
- References
- 53
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 14 · 2023: 8 · 2022: 18 · 2021: 13 · 2020: 15 · 2019: 17 · 2018: 19 · 2017: 11 · 2016: 11 · 2015: 9 · 2014: 2
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- ANGPTL4, acute exercise, free fatty acids, PPARδ, AMPK, lipoprotein lipase, lipid metabolism, energy metabolism, lipid homeostasis
- MeSH terms
- Angiopoietin-Like Protein 4, Adult, Fatty Acids, Fluorescent Antibody Technique, Homeostasis, Humans, Male, Middle Aged, Exercise, Muscle, Skeletal, Angiopoietins, Microarray Analysis, Lipid Metabolism
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