Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice

FEBS Lett. 2018 Jan;592(2):219-232. doi: 10.1002/1873-3468.12940. Epub 2018 Jan 4.

Abstract

The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD-/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD-/- mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation. Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process.

Keywords: metabolic regulation; mitochondrial fatty acid biosynthesis; β-oxidation.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency*
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Animals
  • Cell Plasticity
  • Congenital Bone Marrow Failure Syndromes
  • Disease Models, Animal
  • Fatty Acids / biosynthesis*
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Mice
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / metabolism*
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscular Diseases / metabolism*
  • Triglycerides / administration & dosage

Substances

  • Fatty Acids
  • Triglycerides
  • Acyl-CoA Dehydrogenase, Long-Chain

Supplementary concepts

  • VLCAD deficiency