期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 5, 页码 1384-1389出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409451102
关键词
Acc2(-I-) mutant; acetyl-CoA; carboxylase2; malonyl-CoA
资金
- NIGMS NIH HHS [R01 GM063115, GM-63115] Funding Source: Medline
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 [C-14]palmitate in adipocytes of Acc2(-/-) mutant mice was approximate to80% 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.
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