Ketogenic diet ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle by alleviating endoplasmic reticulum stress

作者全名："Ma, Qin; Jiang, Lincheng; You, Yuehua; Ni, Hongbing; Ma, Li; Lin, Xiaojing; Wang, Zhuyun; Yan, Weiyan; Xiao, Xiaoqiu; Li, Xinyu; Li, Jibin"

作者地址："[Ma, Qin; Jiang, Lincheng; Li, Jibin] Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing 400016, Peoples R China; [Ma, Qin; Jiang, Lincheng; You, Yuehua; Ni, Hongbing; Ma, Li; Lin, Xiaojing; Wang, Zhuyun; Yan, Weiyan; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing 400016, Peoples R China; [You, Yuehua; Ni, Hongbing; Ma, Li; Lin, Xiaojing; Wang, Zhuyun; Yan, Weiyan; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Chongqing 400016, Peoples R China; [Li, Xinyu] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China"

通信作者："Li, JB (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing 400016, Peoples R China.; Li, XY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001183544700001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：702

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Endoplasmic reticulum stress; beta-hydroxybutyrate; Glucose transporter type 4; Insulin resistance

摘要："Objective: Ketogenic diets (KD) have been shown to alleviate insulin resistance (IR) by exerting anti-lipogenic and insulin sensitizing effects in the liver through a variety of pathways. The present study sought to investigate whether a ketogenic diet also improves insulin sensitization in skeletal muscle cells through alleviating endoplasmic reticulum stress. Methods: High-fat diet-induced IR mice were allowed to a 2-week ketogenic diet. Insulin resistance and glucose tolerance were evaluated through GTT, ITT, and HOMA-IR. The C2C12 myoblasts exposed to palmitic acid were used to evaluate the insulin sensitization effects of beta-hydroxybutyric acid (beta-OHB). Molecular mechanisms concerning ER stress signaling activation and glucose uptake were assessed. Results: The AKT/GSK3 beta pathway was inhibited, ER stress signaling associated with IRE1, PERK, and BIP was activated, and the number of Glut4 proteins translocated to membrane decreased in the muscle of HFD mice. However, all these changes were reversed after 2 weeks of feeding on a ketogenic diet. Consistently in C2C12 myoblasts, the AKT/GSK3 beta pathway was inhibited by palmitic acid (PA) treatment. The endoplasmic reticulum stress-related proteins, IRE1, and BIP were increased, and the number of Glut4 proteins on the cell membrane decreased. However, beta-OHB treatment alleviated ER stress and improved the glucose uptake of C2C12 cells. Conclusion: Our data reveal that KD ameliorated HFD-induced insulin resistance in skeletal muscle, which was partially mediated by inhibiting endoplasmic reticulum stress. The insulin sensitization effect of beta-OHB is associated with up regulation of AKT/GSK3 beta pathway and the increase in the number of Glut4 proteins on the cell membrane."

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