Abstract

High-fat diet (HFD)-induced metabolic syndrome followed by chronic kidney disease (CKD) have received extensive attention. However, the pathogenesis that contributes to HFD-induced renal injury still remains unclear. Transmembrane protein 126B (Tmem126b) is a complex I assembly factor, playing critical role in controlling important biological processes . In the study, we showed that Tmem126b levels were increased in kidney of HFD-fed mice. Tmem126b knockout (KO) attenuated metabolic disorders in mice challenged with HFD. Further, Tmem126b-KO mice showed alleviated kidney damage in response to HFD treatment. Mechanistically, we suggested that in kidney of mice, the dyslipidemia , apoptosis, and mitochondria dysfunction generated by HFD were prevented by Tmem126b deletion via regulating the expression of associated signals. Further, we demonstrated that HFD-induced renal inflammation was ameliorated by Tmem126b knockout, as evidenced by the down-regulated expression of inflammatory factors, including tumor necrosis factor a (TNF-α), interleukin (IL)-6, IL-1β and monocyte chemotactic protein (MCP)-1, which was through repressing nuclear factor kappa B (NF-κB) signaling pathways . Additionally, Tmem126b ablation repressed oxidative stress in renal samples of HFD-fed mice partly by promoting nuclear factor-erythroid 2 related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) expression. The role of Tmem126b knockout in protecting against HFD-triggered renal injury was verified in palmitate (PA)-incubated cells with Tmem126b knockdown. Importantly, inhibiting Nrf-2 expression abolished Tmem126b knockdown-alleviated lipid deposition , apoptosis, inflammation, ROS generation and mitochondrial dysfunction. Collectively, our study identified Tmem126b as a positive regulator for the progression of CKD induced by HFD through meditating Nrf-2 expression.