Abstract
Sirt1 plays an important role in regulating glucose and lipid metabolism in obese animal models. Impaired adipose tissue angiogenesis in the obese state decreases adipogenesis and thereby contributes to glucose intolerance and lipid metabolism. However, the mechanism by which Sirt1 activation affects obesity-associated impairments in angiogenesis in the adipose tissue is not fully understood. Here, we show that SRT1720 treatment induces angiogenic genes in cultured 3T3-L1 preadipocytes and ex vivo preadipocytes. siRNA-mediated knockdown of Sirt1 in 3T3-L1 preadipocytes downregulated angiogenic genes in the preadipocytes. SRT1720 treatment upregulated metabolically favorable genes and reduced inflammatory gene expressions in the adipose tissue of diet-induced obese (DIO) mice. Collectively, these findings suggest a novel role of SRT1720-induced Sirt1 activation in the induction of angiogenic genes in preadipocytes, thereby reducing inflammation and fibrosis in white adipose tissue (WAT) and promoting insulin sensitivity.
Highlights
Sirt[1] plays an important role in regulating glucose and lipid metabolism in obese animal models
The expression of the angiogenic genes was downregulated in the Sirt1-knockdown 3T3-L1 preadipocytes (Figs 1B and S2), suggesting that Sirt[1] is directly involved in the promotion of angiogenesis in preadipocytes
We found that SRT1720 treatment augmented the expression of angiogenic genes in an ex vivo adipose tissue-derived stem cells (ASCs) culture (Fig. 1C), showing that SRT1720 induces angiogenic genes in the preadipocytes
Summary
Sirt[1] plays an important role in regulating glucose and lipid metabolism in obese animal models. Impaired adipose tissue angiogenesis in the obese state decreases adipogenesis and thereby contributes to glucose intolerance and lipid metabolism. SRT1720 treatment upregulated metabolically favorable genes and reduced inflammatory gene expressions in the adipose tissue of diet-induced obese (DIO) mice These findings suggest a novel role of SRT1720-induced Sirt[1] activation in the induction of angiogenic genes in preadipocytes, thereby reducing inflammation and fibrosis in white adipose tissue (WAT) and promoting insulin sensitivity. The administration of resveratrol, a polyphenol known to be a Sirt[1] activator, improves glucose metabolism with increased fatty acid oxidation in skeletal muscle and the up-regulation of mitochondrial genes in the liver[3,15]. SRT1720 improves insulin sensitivity in DIO mice by increasing fatty acid oxidation in skeletal muscle, liver and brown adipose tissue[11]. We examined the effect of SRT1720 treatment on the expression of angiogenic genes in preadipocytes
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