Evaluation of the Effects of High Uric Acid on Glucolipid Metabolism, Renal Injury and the Gut Microbiota in Diabetic Hamsters with Dyslipidemia

The prevalence of hyperuricemia, a metabolic disturbance associated with elevated serum uric acid (UA), is increasing worldwide. High UA is closely related to increased risk for chronic renal disease, diabetes, abnormal lipid metabolism and abnormal gut microbiota. However, the effects of high UA on patients with diabetes and dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in hamsters to evaluate the effects of high UA on glucolipid metabolism, renal injury and the gut microbiota. Our results indicated that a low-dose streptozotocin and diet-induced diabetic hamster model with hyperuricemia and dyslipidemia was successively established by the combination of intragastric potassium oxonate (PO) and adenine, the intake of fructose water and high-fat/cholesterol diet. PO treatment and a high-fat/cholesterol diet had synergistic effects on increasing UA, urea nitrogen, and creatinine levels, hepatic XOD activity, PAI-1 and TGF-β expressions, and the relative abundance of Lleibacterium, causing the moderate tubular degeneration, tubular atrophy, inflammatory cell infiltration, urate deposition, protein casts, and accelerated renal injury in diabetic hamsters. High UA was closely related to decreased antioxidant capacity; decreased renal VEGF expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes (F/B) ratios; and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. However, elevated UA levels alone had negligible effects on serum glucose, insulin, weight loss, organ indices, intestinal flora richness and bacterial community diversity in diabetic hamsters. High UA levels in diabetic hamsters with hyperuricemia and dyslipidemia were positively associated with Bacteroides, unclassified _f_Ruminococcaceae, Candidatus_Saccharimonas, norank_f_Muribaculaceae, Prevotellaceae_NK3B31_group, and Prevotelaceae_UCG-001 levels and negatively associated with Helicobacterium. Therefore, each intestinal microbe associated signaling pathway affecting UA metabolism and the health of the animal host still needs to be identified in future studies to identify new drug targets for the treatment of hyperuricemia and dyslipidemia in patients with diabetes.