6‐Gingerol induces browning of white adipose tissue to improve obesity through PI3K/AKT‐RPS6‐mediated thermogenesis pathway

The browning of white fat has become a hot topic as it could help to lose weight and improve metabolic health. Therefore, this study aims explore the in vivo or thermogenesis effect 6-gingerol (6G), natural bioactive compound ginger, clarify underlying mechanism. results showed that 6G limited gain, improved cold tolerance, increased energy expenditure high-fat diet-induced obese mice. Moreover, histological immunohistochemical analysis revealed activated brown adipose tissue (BAT) induced more beige cells epididymal (eWAT). Meanwhile, eWAT was marked by appearance multilocular lipid droplets, higher level uncoupling protein 1 (UCP1), mitochondrial content. potential molecular mechanism further investigated RNA-seq, qPCR, western blot assays. Results indicated significantly expression thermogenesis-specific markers triggers mainly through phosphoinositide 3-kinase (PI3K) / kinase B (AKT)-ribosomal S6 (RPS6) axis. Consistently, vitro, data pretreatment primary adipocytes with PI3K/AKT pathway inhibitor counteracted 6G-induced effects. This reveals, for first time, induces modulating PI3K/AKT-RPS6 pathways, thereby alleviating obesity.