First Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
Department of Metabolism and Nutrition, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
Sci Rep. 2018 Jul 27;8(1):11370. doi: 10.1038/s41598-018-29773-0.
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.
Sirt1 在调节肥胖动物模型中的葡萄糖和脂质代谢方面发挥着重要作用。肥胖状态下脂肪组织血管生成受损会减少脂肪生成，从而导致葡萄糖耐量受损和脂质代谢异常。然而，Sirt1 激活影响脂肪组织中与肥胖相关的血管生成受损的机制尚不完全清楚。在这里，我们表明 SRT1720 处理可诱导培养的 3T3-L1 前体脂肪细胞和离体前体脂肪细胞中的血管生成基因。3T3-L1 前体脂肪细胞中的 Sirt1 的 siRNA 介导的敲低会下调前体脂肪细胞中的血管生成基因。SRT1720 处理可上调代谢有利的基因，并降低饮食诱导肥胖 (DIO) 小鼠脂肪组织中的炎症基因表达。总的来说，这些发现表明 SRT1720 诱导的 Sirt1 激活在诱导前体脂肪细胞中的血管生成基因中的新作用，从而减少白色脂肪组织 (WAT) 中的炎症和纤维化，并促进胰岛素敏感性。
