Abstract
Aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective SGLT-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and NLRP-3 inflammasome activation, which has never been investigated so far. Male C57BL/6 mice were fed control or a High Fat High Sugar (HFHS) diet for 4 months. Over the last 2 months, subsets of animals were treated with empagliflozin (1-10 mg/kg) added to the diet. Empagliflozin evoked body weight reduction (p<0.001 for the highest dose) and positive effects on fasting glycaemia and HOMA IR index. In addition, the drug was able to reduce renal tubular damage and liver triglycerides level in a dose-dependent manner. Interestingly, empagliflozin also decreased cardiac lipid accumulation. Moreover, diet-induced activation of NLRP-3 in kidney and liver (not observed in the heart) was dose-dependently attenuated by empagliflozin. Our results clearly demonstrate the ability of empagliflozin to counteract the deleterious effects evoked by chronic exposure to HFHS diet. Most notably, empagliflozin treatment was associated with NLRP-3 inflammasome signaling modulation, suggesting that this inhibition may contribute to the drug therapeutic effects.
- The American Society for Pharmacology and Experimental Therapeutics