Benfotiamine attenuates the high-carbohydrate diet-induced mitochondrial redox imbalance in fish Megalobrama amblycephala by activating SIRT3

Fish are carbohydrates-intolerant, thus generally exhibiting metabolic disorders and mitochondrial dysfunctions to high-carbohydrate (HC) diets. Benfotiamine is a lipid-soluble derivative of vitamin B1, which can reduce oxidative stress, improve the function of glycolysis, and play a high biological effect, while the underlying mechanisms still remains unclear. This study aimed to investigate the effects of benfotiamine on the mito-chondrial oxidative stress of carp Megalobrama amblycephala subjected to HC treatment both in vivo and in vitro. In vivo, fish were randomly fed a control diet, a HC diet, and a HC diet supplemented with benfotiamine respectively for 12 weeks. In the first vitro study, primary hepatocytes were cultured with media, high-glucose (HG), and HG supplemented with benfotiamine, respectively. In the second vitro study, hepatocytes were treated by media, vehicle, HG, HG + honokiol (the agonist of SIRT3), respectively. HC/HG induced mitochondrial oxidative stress of fish, as was evidenced by the increased ROS and MDA contents coupled with the decreased CAT, GSH-Px and MnSOD activities, and the decreased SIRT3 and SOD2 contents. However, benfotiamine sup-plementation exhibited opposite effects, as also held true after the treatment of honokiol. Overall, the results suggested that benfotiamine could alleviate the mitochondrial oxidative stress of fish subjected to HG/HC treatment by activating SIRT3.