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Targeting ACC to Stay Lean

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Science  02 Nov 2007:
Vol. 318, Issue 5851, pp. 717
DOI: 10.1126/science.318.5851.717g

Acetyl-CoA carboxylase (ACC) regulates the synthesis and degradation of fatty acids, and mice lacking the ACC2 isoform are leaner than wild-type animals. Choi et al. have characterized the whole-body energy metabolism and insulin sensitivity of ACC2/ mice. By monitoring activity, food consumption, and energy expenditure, they showed that ACC2/ animals ate more food than did wild-type animals but remained smaller. The ACC2/ animals were also resistant to obesity induced by giving them a high-fat diet. These results could be explained by the increase in energy expenditure observed in the knockout animals, which is consistent with the increase in oxidation of both fats and carbohydrates in ACC2/ animals. The resistance to insulin that occurs with fat accumulation is thought to result from the accumulation of diacylglycerol in muscle and liver and the consequent activation of protein kinase C (PKC) q and PKCe in muscle and liver, respectively. ACC2/ mice displayed an enhanced sensitivity to insulin that was associated with decreased activity of the PKC enzymes. Although ACC2 is not a particularly easy target for small-molecule drugs, the development of a specific inhibitor could improve the treatment of diabetes and obesity.— LBR

Proc. Natl. Acad. Sci. U.S.A. 104 16480 (2007).

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