Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models

Eugene F. Diekman, Michel Van Weeghel, Ronald J.A. Wanders, Gepke Visser, Sander M. Houten

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD-/-; VLCAD+/-) in addition to a validated mouse model (LCAD-/-; VLCAD+/+) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD∼ ; VLCAD+ mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.

Original languageEnglish
Pages (from-to)2891-2900
Number of pages10
JournalFASEB Journal
Volume28
Issue number7
DOIs
StatePublished - 1 Jul 2014

Keywords

  • Creatine kinase
  • Myopathy
  • Rhabdomyolysis
  • Thermogenesis

Fingerprint

Dive into the research topics of 'Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models'. Together they form a unique fingerprint.

Cite this