Abstract
Malonyl-coenzyme A (malonyl-CoA), generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the regulation of energy homeostasis. Here, we show that Acc2-/- mutant mice have a normal life span, a higher fatty acid oxidation rate, and lower amounts of fat. In comparison to the wild type, Acc2-deficient mice had 10- and 30-fold lower levels of malonyl-CoA in heart and muscle, respectively. The fatty acid oxidation rate in the soleus muscle of the Acc2-/- mice was 30% higher than that of wild-type mice and was not affected by addition of insulin; however, addition of insulin to the wild-type muscle reduced fatty acid oxidation by 45%. The mutant mice accumulated 50% less fat in their adipose tissue than did wild-type mice. These results raise the possibility that pharmacological manipulation of ACC2 may lead to loss of body fat in the context of normal caloric intake.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3-Hydroxybutyric Acid / blood
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Acetyl-CoA Carboxylase / deficiency
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Acetyl-CoA Carboxylase / genetics
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Acetyl-CoA Carboxylase / metabolism*
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Adipose Tissue / metabolism*
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Animals
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Blood Glucose / metabolism
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Body Weight
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Cholesterol / blood
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Energy Intake
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Fasting
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Fatty Acids / blood
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Fatty Acids / metabolism*
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Female
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Gene Targeting
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Insulin / pharmacology
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Lipid Metabolism*
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Liver / enzymology
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Liver / metabolism
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Liver Glycogen / metabolism
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Malonyl Coenzyme A / metabolism*
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Mice
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Mitochondria, Liver / enzymology
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Muscle, Skeletal / enzymology
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Muscle, Skeletal / metabolism
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Mutation
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Myocardium / enzymology
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Myocardium / metabolism
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Oxidation-Reduction
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Palmitic Acid / metabolism
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Triglycerides / blood
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Weight Gain
Substances
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Blood Glucose
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Fatty Acids
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Insulin
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Liver Glycogen
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Triglycerides
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Palmitic Acid
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Malonyl Coenzyme A
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Cholesterol
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Acetyl-CoA Carboxylase
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3-Hydroxybutyric Acid