Brown adipose tissue function in short-chain acyl-CoA dehydrogenase deficient mice.
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.
Skilling
Helen
H
Department of Pediatrics, The Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Coen
Paul M
PM
Fairfull
Liane
L
Ferrell
Robert E
RE
Goodpaster
Bret H
BH
Vockley
Jerry
J
Goetzman
Eric S
ES
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D044926:Butyryl-CoA Dehydrogenase / Q000235:genetics*; D003080:Cold Temperature; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D012768:Shivering / Q000235:genetics; D022722:Thermogenesis / Q000235:genetics*; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000242:Cyclic AMP; D044926:Butyryl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine