Sodium butyrate protects against oxidative stress in high‐fat‐diet‐induced obese rats by promoting GSK‐3β/Nrf2 signaling pathway and mitochondrial function

Abstract

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague-Dawley rats were divided into the control group, obesity-prone (OP) group and obesity-resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high-fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo-1, and Ho-1, but downregulated Gsk-3β mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs-1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. Practical applicationsThis study found that obesity-prone and obesity-resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile.

Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats

“…Nonetheless, excess nutrient supply profoundly enhances oxidative stress and mitochondrial alteration, therefore inevitably driving-regardless of dietary composition itself-metabolic dysfunction during extreme diets. This is a condition that could be improved via supplementation with specific molecules such as short-chain fatty acids or N-acylethanolamines [19,20]. On this point, exploring the impact of oxidative stress and antioxidant barrier potential in MetS, induced in the HFD rat model, would suggest important insights and trace paths for developing prevention approaches [21].…”

Sodium Butyrate Alleviates Free Fatty Acid-Induced Steatosis in Primary Chicken Hepatocytes via Regulating the ROS/GPX4/Ferroptosis Pathway

“…Butyrate, traditionally recognized as an energy substrate, is a short-chain fatty acid generated by the condensation of two acetyl-CoA molecules, forming acetoacetyl-CoA, which is then reduced to butyryl-CoA [28]. Recent investigations have indicated that NaB may mitigate hepatic steatosis, enhance respiratory capacity, and rectify mitochondrial dysfunction in obese mice [29]. Moreover, the administration of NaB in a protective coating prevented the accumulation of fat in the livers and abdominal fat tissues of broilers, while also significantly decreasing the buildup of adipocytic fat in chicken preadipocytes [19].…”