Brown adipose tissue function in short-chain acyl-CoA dehydrogenase deficient mice.

Abstract

Brown adipose tissue is a highly specialized organ that uses mitochondrial fatty acid oxidation to fuel non-shivering thermogenesis. In mice, mutations in the acyl-CoA dehydrogenase family of fatty acid oxidation genes are associated with sensitivity to cold. Brown adipose tissue function has not previously been characterized in these knockout strains. Short-chain acyl-CoA dehydrogenase (SCAD) deficient mice were found to have increased brown adipose tissue mass as well as modest cardiac hypertrophy. Uncoupling protein-1 was reduced by 70% in brown adipose tissue and this was not due to a change in mitochondrial number, nor was it due to decreased signal transduction through protein kinase A which is known to be a major regulator of uncoupling protein-1 expression. PKA activity and in vitro lipolysis were normal in brown adipose tissue, although in white adipose tissue a modest increase in basal lipolysis was seen in SCAD-/- mice. Finally, an in vivo norepinephrine challenge of brown adipose tissue thermogenesis revealed normal heat production in SCAD-/- mice. These results suggest that reduced brown adipose tissue function is not the major factor causing cold sensitivity in acyl-CoA dehydrogenase knockout strains. We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved.

• Authors: Helen Skilling, Paul M Coen, Liane Fairfull, Robert E Ferrell, Bret H Goodpaster, Jerry Vockley, Eric S Goetzman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 400 Issue 3 Pg. 318-22 (Sep 24 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20727852 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Ion Channels
• Mitochondrial Proteins
• Ucp1 protein, mouse
• Uncoupling Protein 1
• Cyclic AMP
• Butyryl-CoA Dehydrogenase
• Acyl-CoA Dehydrogenase, Long-Chain
• Cyclic AMP-Dependent Protein Kinases
• Norepinephrine

Topics

• Acyl-CoA Dehydrogenase, Long-Chain (genetics)
• Adipose Tissue, Brown (drug effects, enzymology, physiology)
• Animals
• Butyryl-CoA Dehydrogenase (genetics)
• Cold Temperature
• Cyclic AMP (pharmacology)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Ion Channels (metabolism)
• Lipolysis (genetics)
• Mice
• Mice, Knockout
• Mitochondrial Proteins (metabolism)
• Norepinephrine (pharmacology)
• Shivering (genetics)
• Thermogenesis (genetics)
• Uncoupling Protein 1