Vitamin D3 Alleviates High-Fat Diet–Induced Endoplasmic Reticulum Stress and Insulin Resistance in Mice

Abstract

Endoplasmic reticulum stress (ERs) may be a key mechanism for the connection of obesity, chronic inflammation, and insulin resistance (IR). As we know, vitamin D3 deficiency is prevalent in obese patients, and it may be an independent risk factor for obesity-induced IR and type 2 diabetes mellitus (T2DM). However, the effects of vitamin D3 on ERs, inflammatory response, and IR were still unknown. This study investigate the effects of vitamin D3 on ERs, inflammatory response, and IR in high-fat-diet (HFD) induced obese mice. Eighty male C57BL/6 mice were randomly divided into four group, including control group (n = 20), HFD group, HFD + low dose (50 IU/kg) of vitamin D3 group (VitD-L), HFD + high dose (250 IU/kg) of vitamin D3 group (VitD-H). The control group was fed with common feed, and the other groups were fed with HFD. After the establishment of the obesity model, the mice in experimental group was fed with different dose of vitamin D3 for 1 week. Then western blot was used to detect the protein expression level of Bip, IRE1, PERK and NF-κB in adipose tissue; serum levels of TNF-α, IL-6, serum 25-hydroxyvitamin D3, fasting blood glucose, glycosylated hemoglobin, triacylglyceride and fasting insulin were measured and the insulin resistance index was calculated. The results indicated that vitamin D3 in both low and high dose could significantly down-regulate the expression level of Bip, IRE1 and PERK, and decrease the expression levels of NF-κB, TNF-α, and IL-6 (p < 0.05). It could also significantly decrease the levels of fasting blood glucose, glycosylated hemoglobin, triacylglyceride and fasting insulin in obese mice (p < 0.05), and significantly alleviate the insulin resistance phenomenon in obese mice. The results indicated that vitamin D3 supplementation could reduce the synthesis and release of inflammatory factors, alleviate endoplasmic reticulum stress and insulin resistance. Disclosure L. Liu: None. X. Li: None.