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Mitochondrial function and dysfunction in exercise and insulin resistance

Publication: Applied Physiology, Nutrition, and Metabolism
13 May 2009

Abstract

Fatty acid translocase (FAT/CD36) represents a novel flexible regulatory system, influencing rates of mitochondrial fatty acid metabolism in both human and rodent skeletal muscle. During exercise, the subcellular redistribution of FAT/CD36 provides a mechanism to increase not only plasma membrane fatty acid transport, but also mitochondrial fatty acid oxidation. This FAT/CD36-mediated coordination of long chain fatty acid (LCFA) transport and oxidation is an intriguing model in the context of insulin resistance. It was believed for almost a decade that reductions in fatty acid oxidation increased intramuscular lipids, thereby contributing to insulin resistance. A reduction in mitochondrial content may reduce the capacity of skeletal muscle LCFA oxidation; however, work from my laboratory has shown that, in some insulin-resistant muscles, mitochondrial content and fatty acid oxidation are both increased, yet these muscles accumulate lipids because of a considerably greater increase in fatty acid transport. Therefore, an alternative model is being considered, in which the balance between LCFA uptake and oxidation is a determining factor in the development of insulin resistance. A permanent redistribution of the LCFA transport protein FAT/CD36 to the sarcolemmal has been consistently found, which results in an increased rate of LCFA transport. This work suggests that the accumulation of skeletal muscle lipids, regardless of changes in mitochondria, is attributable to an increased rate of LCFA transport that exceeds the capacity for oxidation.

Résumé

Le FAT/CD36 apparaît comme un attrayant système flexible de contrôle de la vitesse du métabolisme des graisses dans la mitochondrie tant dans le muscle squelettique de l’humain que du rongeur. Au cours d’un exercice physique, la redistribution subcellulaire du FAT/CD36 donne lieu à un mécanisme qui accroît non seulement le transport des acides gras dans la membrane plasmique, mais aussi l’oxydation des acides gras dans la mitochondrie. La coordination du transport et de l’oxydation des LCFA exercée par le FAT/CD36 constitue un modèle étonnant en présence d’insulinorésistance. Durant tout près de dix ans, on a cru que la diminution de l’oxydation des acides gras augmentait la quantité de lipides intramusculaires et, de ce fait, stimulait l’insulinorésistance. La diminution du contenu mitochondrial peut diminuer la capacité d’oxydation des LCFA dans le muscle squelettique, mais nos observations indiquent une « augmentation » du contenu mitochondrial et de l’oxydation des acides gras dans certains muscles insulinorésistants; pourtant, la quantité de lipides augmente dans ces derniers à cause d’un transport beaucoup plus grand d’acides gras. Ainsi, nous commençons à envisager un autre modèle selon lequel l’équilibre entre la captation et l’oxydation des LCFA est un important facteur du développement de l’insulinorésistance. Systématiquement, nous observons une redistribution permanente du FAT/CD36, la protéine de transport des LCFA dans le sarcolemme, ce qui a pour effet d’accroître le transport des LCFA. D’après nos travaux, l’accumulation des lipides dans le muscle squelettique est due à une augmentation du transport de LCFA qui dépasse la capacité d’oxydation, et ce, quelles que soient les modifications au niveau de la mitochondrie.

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Published In

cover image Applied Physiology, Nutrition, and Metabolism
Applied Physiology, Nutrition, and Metabolism
Volume 34Number 3June 2009
Pages: 440 - 446

History

Received: 24 February 2009
Accepted: 24 February 2009
Version of record online: 13 May 2009

Notes

This paper article is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

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Key Words

  1. mitochondria
  2. fatty acid oxidation
  3. obesity
  4. insulin resistance
  5. mitochondrial biogenesis
  6. plasma membrane transport

Mots-clés

  1. mitochondrie
  2. oxydation des acides gras
  3. obésité
  4. insulinorésistance
  5. biogenèse mitochondriale
  6. transport membranaire

Authors

Affiliations

Graham P. Holloway (email: [email protected])
Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada (e-mail: (email: [email protected])).

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