Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2

• Published in: Science (American Association for the Advancement of Science) 2001-03, Vol.291 (5513), p.2613-2616
• Main Authors: Abu-Elheiga, Lutfi, Matzuk, Martin M., Khaled A. H. Abo-Hashema, Wakil, Salih J.
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - blood; Acetyl-CoA Carboxylase - deficiency; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; acetyl-CoA carboxylase 2; Adipose Tissue - metabolism; Adipose tissues; Analytical, structural and metabolic biochemistry; Animals; Bioenergetics; Biological and medical sciences; Blood Glucose - metabolism; Body Weight; Cholesterol - blood; Energy Intake; Energy metabolism; Enzymes; Enzymes and enzyme inhibitors; Fasting; Fatty acid metabolism; Fatty acids; Fatty Acids - blood; Fatty Acids - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Targeting; Glycogen; Habitat conservation; Insulin - pharmacology; Ligases; Lipid Metabolism; Lipids; Liver; Liver - enzymology; Liver - metabolism; Liver Glycogen - metabolism; Malonyl Coenzyme A - metabolism; Metabolism; Mice; Mitochondria, Liver - enzymology; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscles; Mutation; Myocardium; Myocardium - enzymology; Myocardium - metabolism; Oxidation; Oxidation-Reduction; Palmitic Acid - metabolism; Rodents; Triglycerides - blood; Weight Gain
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1056843

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.