Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice.
Acc2-/- mutant mice, when fed a high-fat/high-carbohydrate (HF/HC) diet, were protected against diet-induced obesity and diabetes. To investigate the role of acetyl-CoA carboxylase 2 (ACC2) in the regulation of energy metabolism in adipose tissues, we studied fatty acid and glucose oxidation in primary cultures of adipocytes isolated from wild-type and Acc2-/- mutant mice fed either normal chow or a HF/HC diet. When fed normal chow, oxidation of [14C]palmitate in adipocytes of Acc2-/- mutant mice was approximately 80% higher than in adipocytes of WT mice, and it remained significantly higher in the presence of insulin. Interestingly, in addition to increased fatty acid oxidation, we also observed increased glucose oxidation in adipocytes of Acc2-/- mutant mice compared with that of WT mice. When fed a HF/HC diet for 4-5 months, adipocytes of Acc2-/- mutant mice maintained a 25% higher palmitate oxidation and a 2-fold higher glucose oxidation than WT mice. The mRNA level of glucose transporter 4 (GLUT4) decreased several fold in the adipose tissue of WT mice fed a HF/HC diet; however, in the adipose tissue of Acc2-/- mutant mice, it was 7-fold higher. Moreover, lipolysis activity was higher in adipocytes of Acc2-/- mutant mice compared with that in WT mice. These findings suggest that continuous fatty acid oxidation in the adipocytes of Acc2-/- mutant mice, combined with a higher level of glucose oxidation and a higher rate of lipolysis, are major factors leading to efficient maintenance of insulin sensitivity and leaner Acc2-/- mutant mice.
Oh
Wonkeun
W
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abu-Elheiga
Lutfi
L
Kordari
Parichher
P
Gu
Zeiwei
Z
Shaikenov
Tattym
T
Chirala
Subrahmanyam S
SS
Wakil
Salih J
SJ
D000103:Acetyl-CoA Carboxylase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000201:enzymology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D004822:Epididymis; D005947:Glucose / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D008316:Malonyl Coenzyme A; C498191:Acacb protein, mouse; D000103:Acetyl-CoA Carboxylase; D005947:Glucose