title: Disrupted fat distribution and composition due to medium-chain triglycerides in mice with a β-oxidation defect.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany. sara.tucci@med.uni-duesseldorf.de
authors.forename: Sara
authors.initials: S
authors.lastname: Tucci
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flögel
authors.forename: Marga
authors.initials: M
authors.lastname: Sturm
authors.forename: Elena
authors.initials: E
authors.lastname: Borsch
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D050218:Body Fat Distribution; D000080984:Congenital Bone Marrow Failure Syndromes; D005230:Fatty Acids, Nonesterified / Q000097:blood; D050356:Lipid Metabolism; D008052:Lipid Metabolism, Inborn Errors; D008099:Liver / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D028361:Mitochondrial Diseases / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014280:Triglycerides / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D044942:Acyl-CoA Dehydrogenase, Long-Chain