Sodium butyrate protects against oxidative stress between obesity-prone and obesity-resistant rats induced by HFD through modulating Nrf2 pathway and mitochondrial function

Abstract Background Sodium butyrate (NaB) is obtained by fermenting dietary fiber via intestinal microflora and has recently been shown to improve some antioxidant enzymes in vivo. Methods In this study, we investigated the antioxidant effects of Sodium butyrate on obesity rats induced by high-fed diet. Results NaB intervention could effectively reduce the body weight of rats in the obesity-prone(OP) and obesity-resistant(OR)group, and reduce insulin resistance, plasma lipid, protect the gastrocnemius muscle and pancreas from oxidative stress induced by high fat diet, upregulate T-AOC, antioxidant enzyme activity and GSH/GSSG ratio, reduce ROS level and MDA content. NaB may increase Pi3k, Nrf2, Nqo-1, Ho-1 and inhibit Gsk-3β mRNA expression by regulating Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention could significantly increase the expression of Glut4 and Irs-1 mRNA in gastrocnemius muscle of OP and OR rats, suppress the expression of Bax and Caspase 3, increase the mRNA expression of Pdx1, MafA and Bcl-2, and increase insulin secretion and muscle insulin sensitivity. The regulatory effect of NaB was correlated with its significantly increased activity of mitochondrial antioxidant enzymes, mitochondrial membrane potential, NADH/NAD+ ratio, acetyl-CoA and ATP production, Tfam and Pgc-1α expression and mitochondrial DNA copy number. In addition, 6% NaB intervention in OP rats, 4%NaB intervention in OR rats were more significant, indicating that there were dose effects of NaB intervention in different obesity phenotypes. Conclusions NaB activates the Nrf2 antioxidant pathway, enhances the expression level of downstream antioxidant genes, improves the antioxidant capacity of obese rat tissues, and at the same time promotes muscle protein synthesis, improves insulin sensitivity, and promotes glucose metabolism.