Total saponins from Panax japonicus mediate the paracrine interaction between adipocytes and macrophages to promote lipolysis in the adipose tissue during aging via the NLRP3 inflammasome/GDF3/ATGL axis.

Adipocytic lipolysis is strongly related to the increase of visceral fat, decrease of exercise capacity, and various other metabolic syndromes during aging. It is significantly influenced by the paracrine relationship between adipocytes and the adipose tissue macrophages (ATMs), and the cytokines secreted by ATMs have endocrine effects on adjacent tissues. We previously reported that the total saponins from Panax japonicus (TSPJs) can enhance lipid metabolism. In this work, we for the first time proved that TSPJs promoted adipocytic lipolysis by preventing NLRP3 activation in ATMs to inhibit the expression of GDF3. The decrease of GDF3 by TSPJs restored the expression of the adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (p-HSL), both of which are known to decrease with aging. Thus, the NLRP3 inflammasome/GDF3/ATGL axis may be a worthy target in developing future clinical solutions for aging-related obesity.