Introduction: 

Therapeutical approaches in patients with long chain fatty acid oxidation disorders include fat-modified diets, in which long-chain triglycerides are replaced by medium-chain triglycerides (MCT). MCTs are able to bypass the first steps of b-oxidation catalyzed by long chain acyl-CoA dehydrogenases and thus limit metabolic derangements which may cause development of cardiomyopathy and skeletal myopathy. MCTs are considered as safe dietary intervention although long-term observations are still missing.

Methods: 

To investigate the consequences of a prolonged MCT diet we used very-long chain acyl-CoA dehydrogenase deficient (VLCAD^-/-) mice and analyzed the dietary effects on abdominal fat distribution and composition as well as on liver fat by in vivo¹H and ¹³C MR analysis at 9.4 Tesla.

Results: 

We show that MCT supplementation, without increasing the total fat content of the diet, induces a dramatic accumulation of visceral fat and liver lipids in VLCAD^-/- mice when applied over one year. Furthermore, long-term MCT diet leads to a profound shift in body triglyceride composition in that levels of physiological important polyunsaturated fatty acids dramatically decrease. Concomitant to the alterations in fat distribution and composition, we demonstrate severe liver damage in VLCAD^-/- mice with substantial signs of oxidative stress and steatohepatitis. Despite the fact that all MCT-induced effects were exceptionally pronounced in VLCAD^-/- mice, we noted that also wild-type mice displayed a tendency to a similar "fatty" phenotype as VLCAD-deficient mice.

Conclusion: 

In summary, we demonstrate that MCT therapy of mice with a defect in ß-oxidation results in a severe phenotype similar to clinical non-alcoholic steatohepatitis and metabolic syndrome.