Disrupted fat distribution and composition due to medium-chain triglycerides in mice with a β-oxidation defect

Am J Clin Nutr. 2011 Aug;94(2):439-49. doi: 10.3945/ajcn.111.012948. Epub 2011 Jun 22.

Abstract

Background: Because of the enhanced recognition of inherited long-chain fatty acid oxidation disorders by worldwide newborn screening programs, an increasing number of asymptomatic patients receive medium-chain triglyceride (MCT) supplements to prevent the development of cardiomyopathy and myopathy.

Objective: MCT supplementation has been recognized as a safe dietary intervention, but long-term observations into later adulthood are still not available. We investigated the consequences of a prolonged MCT diet on abdominal fat distribution and composition and on liver fat.

Design: Mice with very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD(-/-)) were supplemented for 1 y with a diet in which MCTs replaced long-chain triglycerides without increasing the total fat content. The dietary effects on abdominal fat accumulation and composition were analyzed by in vivo (1)H- and (13)C-magnetic resonance spectroscopy (9.4 Tesla).

Results: After 1 y of MCT supplementation, VLCAD(-/-) mice accumulated massive visceral fat and had a dramatic increase in the concentration of serum free fatty acids. Furthermore, we observed a profound shift in body triglyceride composition, ie, concentrations of physiologically important polyunsaturated fatty acids dramatically decreased. (1)H-Magnetic resonance spectroscopy analysis and histologic evaluation of the liver also showed pronounced fat accumulation and marked oxidative stress.

Conclusion: Although the MCT-supplemented diet has been reported to prevent the development of cardiomyopathy and skeletal myopathy in fatty acid oxidation disorders, our data show that long-term MCT supplementation results in a severe clinical phenotype similar to that of nonalcoholic steatohepatitis and the metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Animals
  • Body Composition*
  • Body Fat Distribution*
  • Congenital Bone Marrow Failure Syndromes
  • Fatty Acids, Nonesterified / blood
  • Lipid Metabolism
  • Lipid Metabolism, Inborn Errors
  • Liver / metabolism
  • Metabolism, Inborn Errors / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Diseases / metabolism*
  • Muscular Diseases / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Triglycerides / administration & dosage*
  • Triglycerides / metabolism

Substances

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

Supplementary concepts

  • VLCAD deficiency