标题：Vitamin D alleviates skeletal muscle loss and insulin resistance by inducing vitamin D receptor expression and regulating the AMPK/SIRT1 signaling pathway in mice
出版社：Sociedade Brasileira de Ciência e Tecnologia de Alimentos
摘要：Vitamin D (VD) was reported to play protective roles in skeletal muscle. This study aimed to explore whether endoplasmic reticulum (ER) stress inhibition is associated with the protective effects of VD/VD receptor (VDR) signaling on skeletal muscle functions. C2C12 skeletal muscle cells were treated with palmitic acid (PA) and then incubated with different concentrations of 1,25-(OH)2-vitamin D3 (VD3), and we found that VD3 improved the impaired cell viability induced by PA and increased VDR expression in a dose-dependent manner. Then 100 nM VD3 treatment and VDR overexpression both ameliorated PA-induced ER stress, apoptosis, inflammation and glucose uptake inhibition in C2C12 myocytes. Furthermore, VDR knockdown reversed the protective effects of VD3 on C2C12 cell functions. Additionally, PA-treated C2C12 cells were treated with VD3 alone or together with AMPK signaling inhibitor Compound C. VD3 promoted phosphorylation of AMPK and SIRT1 expression, while Compound C reversed these effects and abolished the protective effects of VD3 in C2C12 cells. High-fat diet (HFD)-fed mice were treated with VD3, and VD3 alleviated skeletal muscle loss and insulin resistance in mice. In conclusion, VD inhibited AMPK/SIRT1-mediated ER stress by increasing VDR expression, and further ameliorated skeletal muscle loss and insulin resistance in mice.
