Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.

Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four wk, mice fed chow gained 2.3 ± 0.3 g, while HFD mice gained 6.8 ± 0.5 g. After 4 wk, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 wk. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 ± 0.3 g and 3.3 ± 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-α, MCP-1, PAI-1 and IKKβ was increased in adipose tissue from HFD mice compared with chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD.

The goal of this study was to develop a Korean version of the Global Physical Activity Questionnaire (K-GPAQ) and to examine its reliability and validity. The English version of the GPAQ was translated to the Korean language (K-GPAQ) via forward–backward translation. Reliability of the K-GPAQ was evaluated using a one-week interval test–retest method with 115 individuals. Criterion-related validity of the K-GPAQ was examined with 199 participants using accelerometers. Cohen’s kappa and Spearman’s correlation coefficients were used to measure test–retest reliability and validity, respectively. A Bland–Altman analysis was used to assess agreement between physical activity (PA) levels measured via K-GPAQ and the accelerometer. Coefficients for the reliability of the K-GPAQ showed moderate agreement for recreational PA and slight agreement for work-related PA (Cohen’s kappa: 0.60–0.67 for recreational PA and 0.30–0.38 for work-related PA and Spearman’s rho: 0.27–0.47 for work-related PA and 0.53–0.70 for recreational PA). Criterion validity of the total amount of PA, as measured by the K-GPAQ and the accelerometer, showed a weak but significant correlation (r = 0.34, p < 0.01). The K-GPAQ is a reliable and valid questionnaire to measure PA although K-GPAQ overestimated PA levels.