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Selective overexpression of human SIRT1 in adipose tissue enhances energy homeostasis and prevents the deterioration of insulin sensitivity with ageing in mice.
|Title||Selective overexpression of human SIRT1 in adipose tissue enhances energy homeostasis and prevents the deterioration of insulin sensitivity with ageing in mice.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Xu C, Bai B, Fan P, Cai Y, Huang B, Law IK, Liu L, Xu A, Tung C, Li X, Siu F-M, Che C-M, Vanhoutte PM, Wang Y|
|Journal||American journal of translational research|
SIRT1, a longevity regulator and NAD(+)-dependent deacetylase, plays a critical role in promoting metabolic fitness associated with calorie restriction and healthy ageing. Using a tissue-specific transgenic approach, the present study demonstrates that over-expression of human SIRT1 selectively in adipose tissue of mice prevents ageing-induced deterioration of insulin sensitivity and ectopic lipid distribution, reduces whole body fat mass and enhances locomotor activity. During ageing, the water-soluble vitamin biotin is progressively accumulated in adipose tissue. Over-expression of SIRT1 alleviates ageing-associated biotin accumulation and reduces the amount of biotinylated proteins, including acetyl CoA carboxylase, a major reservoir of biotin in adipose tissues. Chronic biotin supplementation increases adipose biotin contents and abolishes adipose SIRT1-mediated beneficial effects on insulin sensitivity, lipid metabolism and locomotor activity. Biochemical, spectrometric and chromatographic analysis revealed that biotin and its metabolites act as competitive inhibitors of SIRT1-mediated deacetylation. In summary, these results demonstrate that adipose SIRT1 is a key player in maintaining systemic energy homeostasis and insulin sensitivity; enhancing its activity solely in adipose tissue can prevent ageing-associated metabolic disorders.
|Alternate Journal||Am J Transl Res|