Rare ginsenosides transformed from stems and leaves of

Background: White adipose tissue (WAT) browning can promote thermogenesis and could be a promising target for treating obesity. Rare ginsenosides transformed from stems and leaves of Methods: Five amino acids were selected as the catalysts for the transformation of ginsenosides into rare ginsenosides. An obese mouse model was established by feeding mice a high-fat diet (HFD) for 14 weeks. The effects of T-GSSL on obese mice were assessed by measuring body weight, fat mass, energy expenditure (EE), and glucose tolerance. The 3T3-L1 cells were differentiated into mature adipocytes and incubated with T-GSSL. Immunohistochemistry, co-immunoprecipitation (Co-IP), enzyme-linked immunosorbent assays (ELISA), western blotting (WB), real-time polymerase chain reaction (PCR), and other methods were used to investigate the targets and mechanisms of action of T-GSSL. Results: Ginsenosides in GSSL were hydrolyzed using glutamic acid as a catalyst and 12 rare ginsenosides were produced, with a total conversion rate of 95 %. T-GSSL ameliorated metabolic disorders, lipid ectopic deposition, and obesity, and maintained glucose homeostasis in obese mice. T-GSSL treatment promoted adipose browning and enhanced EE in both HFD mice and 3T3-L1 cells. These effects were decreased in cells treated with a protein kinase A (PKA) antagonist or subjected to Conclusions: T-GSSL attenuates diet-induced obesity by promoting adipose browning through the inhibition of REGγ and subsequent activation of the PKA/CREB pathway.