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.
Abu-Elheiga
L
L
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Matzuk
M M
MM
Abo-Hashema
K A
KA
Wakil
S J
SJ
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