Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis

• Published in: Biomedicine & pharmacotherapy 2022-08, Vol.152, p.113273-113273, Article 113273
• Main Authors: Zhang, Ya, Wu, Qifang, Liu, Jian, Zhang, Zhongshan, Ma, Xiaojing, Zhang, Yaoyue, Zhu, Jiawen, Thring, Ronald W., Wu, Mingjiang, Gao, Yitian, Tong, Haibin
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Antioxidants - pharmacology; Diabetes Mellitus, Type 2 - drug therapy; Diet, High-Fat - adverse effects; GPx4; Insulin Resistance; Isothiocyanates - pharmacology; Isothiocyanates - therapeutic use; Mice; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress; Sulforaphane; Sulfoxides - pharmacology; Sulfoxides - therapeutic use
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113273

Insulin resistance is a characteristic feature of type 2 diabetes. Sulforaphane (SFN) is a natural antioxidant extracted from the cruciferous vegetables. Recent study reported that SFN exhibits excellent anti-diabetic effects, however, the underlying mechanism is still unclear. This study aimed to investigate the therapeutic effects of SFN on a high-fat diet (HFD)-induced insulin resistance and potential mechanism. SFN was found to effectively reduce body weight, fasting blood glucose and hyperlipidemia, and improve liver function in HFD-fed mice. Furthermore, SFN effectively increased glucose uptake and improved insulin signaling in palmitic acid (PA)-induced HepG2 cells. SFN also led to increased expression of antioxidant genes downstream of Nrf2 and decreased accumulation of lipid peroxides MDA and 4-HNE, both in vivo and in vitro. Further studies revealed that SFN significantly reduced glutathione peroxidase 4 (GPx4) inactivation-mediated oxidative stress by activating the AMPK and Nrf2 signaling pathways. In PA-induced HepG2 cells and flies, the alleviation of insulin resistance by SFN was diminished by GPx4 inhibitor. Taken together, SFN ameliorated HFD-induced insulin resistance by activating the AMPK-Nrf2-GPx4 pathway, providing new insights into SFN as a therapeutic compound for the alleviation of insulin resistance. [Display omitted] •SFN alleviates HFD-induced insulin resistance and lipid peroxide accumulation.•SFN eliminates hepatic ROS by activating AMPK and Nrf2, there by alleviate insulin resistance.•GPx4 plays a key role in the alleviation of insulin resistance in SFN•SFN maintains redox and metabolic homeostasis via an Nrf2/GPx4-dependent manner.