Sirt1 activator induces proangiogenic genes in preadipocytes to rescue insulin resistance in diet-induced obese mice

Sirt1 激活剂诱导前脂肪细胞中的促血管生成基因以挽救饮食诱导的肥胖小鼠的胰岛素抵抗

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作者:Allah Nawaz, Arshad Mehmood, Yukiko Kanatani, Tomonobu Kado, Yoshiko Igarashi, Akiko Takikawa, Seiji Yamamoto, Keisuke Okabe, Takashi Nakagawa, Kunimasa Yagi, Shiho Fujisaka, Kazuyuki Tobe

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.

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