Sodium Butyrate Ameliorated Bile Acid Metabolism in Diabetes Mellitus by PI3K/AKT Signaling Pathway via the Gut-Liver Axis.

The liver and gut play a central role in modulating bile acid metabolism. Our recent study found that supplementation with sodium butyrate (NaB) from microbiota might slow diabetes progression and ameliorate liver function in diabetic mice. The role of NaB in the homeostasis of mitochondrial energy metabolism and bile acid metabolism needs to be investigated further, so this study was conducted by us. We used an ELISA kit to detect biochemical indicators related to mice; HE and PAS were used to stain and analyze tissues; CCK8 was used to detect cell viability; and WB was used to detect related indicators. We found here that NaB administration enormously reduced liver hypertrophy and steatosis in diabetic mice, improved liver and gut function and the release of inflammatory factors in diabetic mice, and ameliorated mitochondrial function both in vitro and in vivo. NaB incubation significantly increased bile acid metabolism-related receptors under diabetic conditions; the intracellular content of enzymes related to liver function was elevated within liver cells. Glucose transport proteins GLUT2 and NaB receptor GPR43 were upregulated by NaB on the cell membrane. The actuation of the intracellular signaling proteins PI3K, AKT, and GSK3 was inhibited by NaB under diabetic conditions. The present study proved that the microbiota metabolite NaB has positive effects on bile acid metabolic homeostasis by promoting mitochondrial energy metabolism in enterocytes and the liver, and the GPR43-PI3K-AKT-GSK3 signaling pathway should contribute to this effect.