PT  - JOURNAL ARTICLE
AU  - Elisa Benetti
AU  - Raffaella Mastrocola
AU  - Giovanna Vitarelli
AU  - Juan Carlos Cutrin
AU  - Debora Nigro
AU  - Fausto Chiazza
AU  - Eric Mayoux
AU  - Massimo Collino
AU  - Roberto Fantozzi
TI  - Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation
AID  - 10.1124/jpet.116.235069
DP  - 2016 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 45--53
VI  - 359
IP  - 1
4099  - http://jpet.aspetjournals.org/content/359/1/45.short
4100  - http://jpet.aspetjournals.org/content/359/1/45.full
SO  - J Pharmacol Exp Ther2016 Oct 01; 359
AB  - The aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective sodium glucose cotransporter-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and nucleotide-binding domain, leucine-rich repeat containing protein (NLRP)-3 inflammasome activation, which have never been investigated to date. 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 &amp;lt; 0.001 for the highest dose) and positive effects on fasting glycemia and homeostasis model assessment of insulin resistance. 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.