Potassium supplementation alleviates age-related activation of NLRP3 inflammasome and insulin resistance

Abstract Dietary sodium and potassium may be associated with insulin resistance. NLRP3 inflammasome plays a role in insulin resistance. However, their modulatory effects during aging remain unclear. Here, we enrolled 60 healthy human subjects and found that aging was significantly associated with elevated PBMC NLRP3 expression, plasma IL-1β, and HOMA-IR. Furthermore, higher IL-1β and HOMA-IR levels correlated positively with 24-hour urinary sodium excretion, but negatively with potassium excretion. To establish causality, we evaluated both young and aged mice fed with normal chow, high-salt, or potassium-supplemented diets. Aging induced NLRP3 inflammasome activation in epididymal white adipose tissue and reduced the glucose infusion rate. More, a high-salt diet exacerbated this age-related insulin resistance, whereas potassium supplementation suppressed inflammasome activation and restored the glucose infusion rate. Crucially, inhibition of NLRP3 with MCC950 protected against age-related insulin resistance and completely abolished the effects of both sodium and potassium. These findings demonstrate that dietary sodium exacerbates age-related insulin resistance via the NLRP3 inflammasome pathway, while potassium plays the opposite role.