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

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.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

• Authors: Eugene F Diekman, Michel van Weeghel, Ronald J A Wanders, Gepke Visser, Sander M Houten
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 28 Issue 7 Pg. 2891-900 (Jul 2014) ISSN: 1530-6860 [Electronic] United States
• PMID: 24648546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © FASEB.

Chemical References

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

Topics

• Acyl-CoA Dehydrogenase, Long-Chain (deficiency, metabolism)
• Animals
• Body Temperature (physiology)
• Cardiomegaly (metabolism, physiopathology)
• Congenital Bone Marrow Failure Syndromes
• Disease Models, Animal
• Energy Metabolism (physiology)
• Fatty Acids (metabolism)
• Fatty Liver (metabolism, physiopathology)
• Fibroblasts (metabolism, pathology)
• Lipid Metabolism, Inborn Errors (metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mitochondrial Diseases (metabolism, physiopathology)
• Motor Activity (physiology)
• Muscular Diseases (metabolism, physiopathology)
• Oxidation-Reduction
• Phenotype
• Rhabdomyolysis (metabolism, physiopathology)