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Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise

Nature Reviews Endocrinology volume 16, pages 683–696 (2020)Cite this article

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Abstract

Both the consumption of a diet rich in fatty acids and exercise training result in similar adaptations in several skeletal muscle proteins. These adaptations are involved in fatty acid uptake and activation within the myocyte, the mitochondrial import of fatty acids and further metabolism of fatty acids by β-oxidation. Fatty acid availability is repeatedly increased postprandially during the day, particularly during high dietary fat intake and also increases during, and after, aerobic exercise. As such, fatty acids are possible signalling candidates that regulate transcription of target genes encoding proteins involved in muscle lipid metabolism. The mechanism of signalling might be direct or indirect targeting of peroxisome proliferator-activated receptors by fatty acid ligands, by fatty acid-induced NAD+-stimulated activation of sirtuin 1 and/or fatty acid-mediated activation of AMP-activated protein kinase. Lactate might also have a role in lipid metabolic adaptations. Obesity is characterized by impairments in fatty acid oxidation capacity, and individuals with obesity show some rigidity in increasing fatty acid oxidation in response to high fat intake. However, individuals with obesity retain improvements in fatty acid oxidation capacity in response to exercise training, thereby highlighting exercise training as a potential method to improve lipid metabolic flexibility in obesity.

Key points

  • Both high fat intake and aerobic exercise training increase the abundance and activity of several lipid metabolic proteins in skeletal muscle related to fatty acid uptake, handling and mitochondrial import.

  • Mitochondrial biogenesis is induced primarily by aerobic exercise training and not by high fat intake in humans, probably due to increased ATP turnover occurring only during exercise.

  • Fatty acid availability seems to be a key signal for adaptations in muscle proteins involved in lipid metabolism as fatty acids act as ligands for peroxisome proliferator-activated receptors and through β-oxidation-driven sirtuin 1 signalling.

  • Obesity is characterized by impairments in fatty acid oxidation capacity, but aerobic exercise training is a potent tool to restore such impairments by induction of lipid metabolic proteins in muscle.

  • An efficient capacity to handle and oxidize fatty acids, and the ability to adapt fatty acid utilization to fatty acid availability, seem to be of great importance for both lipid and glucose homeostasis and insulin action.

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Fig. 1: Skeletal muscle adaptations to high dietary fat intake and aerobic exercise training.
Fig. 2: A model suggesting fatty acids as a signal for lipid metabolism adaptations.

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Acknowledgements

B.K. acknowledges the support of the Danish Medical Research Council, the Lundbeck Research Foundation and the Novo Nordisk Research Foundation. The postdoctoral fellowships of A.M.F. and A.-M.L. were supported by a research grant from the Danish Diabetes Academy (grant number NNF17SA0031406), which was funded by the Novo Nordisk Foundation. A.M.F. acknowledges the further support of the Alfred Benzon Foundation. The authors apologize to all the authors whose contributions to the field could not be cited due to space and reference limitations.

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    Andreas Mæchel Fritzen, Anne-Marie Lundsgaard & Bente Kiens

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Fritzen, A.M., Lundsgaard, AM. & Kiens, B. Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise. Nat Rev Endocrinol 16, 683–696 (2020). https://doi.org/10.1038/s41574-020-0405-1

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