Acetate Administration Ameliorates Streptozotocin-Induced Hyperglycemia and Adipose Tissue Loss

Short-chain fatty acids (SCFAs) are products of gut microbiota through fermentation of soluble fibers. Recent studies have highlighted the beneficial roles of SCFAs in various physiological and pathological conditions, including diabetes. In this study, we applied streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) to investigate the potential role of SCFAs in the pathogenesis of T1DM. We found a significant increase in the abundance of SCFA metabolism-related bacteria in mice surviving after 5 month post-STZ injection (mpi), coupled with improved hyperglycemia. While the expression levels of SCFA receptors, including Ffar2 and Ffar3, were significantly upregulated in the intestine of mice at 5 mpi. Consequently, we employed acetate and propionate gavage, which are two of the most dominant SCFAs in the gut and serum, to explore the physiological roles and molecular mechanisms of SCFAs in the progression of T1DM. We found that mice gavaged with acetate had reduced fasting blood glucose levels and less body weight loss. Body composition analysis indicated that acetate administration prevents STZ-induced white adipose tissue (WAT) loss. At the molecular level, acetate treatment increased the genes involved in fatty acid biosynthesis and decreased the protein levels related to lipid catabolism in WAT. In addition, the structure and diversity of gut microbiota were also recovered after acetate treatment in STZ-induced T1D mice. Taken together, our results indicate that acetate is beneficial for T1DM mice by ameliorating STZ-induced hyperglycemia and adipose loss.