Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2.
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.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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Abu-Elheiga
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Matzuk
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Abo-Hashema
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Wakil
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000103:Acetyl-CoA Carboxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D002149:Energy Intake; D005215:Fasting; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D008112:Liver Glycogen; D014280:Triglycerides; D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; D002784:Cholesterol; D000103:Acetyl-CoA Carboxylase; D020155:3-Hydroxybutyric Acid