Protection Of Betaine Supplementation Against High Fructose-induced Renal Injury And Its Mechanisms In Rats

OBJECTIVE:High-fructose intake induces the generation of inflammatory cytokines (tumor necrosis factor-a, interleukin-1β, interleukin-18, interleukin-6and so on), contributing to renal inflammatory response and tubulointerstitial injury. The tissue inflammatory response also inhibits the insulin signaling pathway and induces lipid accumulation. Betaine has shown to be anti-inflammatory activity and reverse the symptoms induced by inflammation. In this study, we investigated the improvement of betaine on kidney injury and its mechanisms in a model of high-fructose fed ratsMETHODS:Rats were received10%fructose in drinking water per day for4weeks and betaine was supplied at62.5,125and250mg/kg togetherly for an additional4weeks. Uric acid, creatinine and blood urea nitrogen in serum and urine were measured by commercial kits. Triglyceride, total cholesterol, nonestesterified fatty acid in serum and kidney were measured by enzymic methods in rats. Glucose tolerance test and insulin tolerance test were performed to investigate insulin resistance in rats. The levels of tumor necrosis factor-a, interleukin-1β, interleukin-18and interleukin-6from kidney and serum were measured by ELISA methods. The protein levels of insulin receptorsubstrate1/phosphorylation of insulin receptorsubstrate1, protein kinase B/phosphorylation of protein kinase B, renal-specific transporter, organic anion transporters1, organic cation transportor1, organic cation transportor2, nuclear factor-KB/phosphorylation of nuclear factor-KB, the NOD-like receptor protein3, peroxisome proliferators-activated receptor-a, carnitine palmitoyltransferase1, and organic cation/canitine transportor2in kidney were detected by western blotting. Rat kidney tissues were stained with oil-red O reagent and hematoxylin-eosin to observe histopathological changes.RESULTS:Betaine supplement showed a beneficial effect on high fructose-induced renal injury by suppressing renal inflammation in rats, which is relative with the improvement of hyperuricemia, renal dysfunction, insulin resistance, tubulointerstitial injury and lipid accumulation. Betaine can reverse the abnormal levels of renal-specific transporter, glucose transporter9, organic anion transporters1, organic cation transportor1and organic cation transportor2in kidney to keep balance of the urate transport system. Betaine inhibited renal proinflammatory cytokines by the down-regulation of renal NF-κB pathway and NLRP3inflammasome in high-fructose fed rats. In this animal model, betaine reversed renal lipid accumulation by improving kidney PPARa-CPTl-OCTN2pathway.CONCLUSION:These results showed that betaine restored high fructose-induced renal dysfuction, insulin resistance, lipid accumulation, and inflammation by inhibiting the activation of NF-KB and the NLRP3inflammasome in the kidney. These findings of our research laid the experimental foundation for the improvement of betaine on kidney injury induced by high fructose.