Work

Rare ginsenosides transformed from stems and leaves of Panax ginseng reverse obesity by promoting browning of white fat through PKA/CREB pathway via REGγ negative regulation

Year: 2024

Type: article

Abstract: 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 Panax ginseng (T-GSSL) exhibit numerous biological activities. However, its potential anti-obesity effects and underlying mechanism remain largely unknown. 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. 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 PKAcα knockdown, whereas they were increased in REGγ −/− mice. The inhibition of REGγ alongside the activation of the PKA/CREB pathway elucidates the mechanism through which T-GSSL reverses obesity by promoting the browning of adipose tissue. T-GSSL attenuates diet-induced obesity by promoting adipose browning through the inhibition of REGγ and subsequent activation of the PKA/CREB pathway. • Ginsenosides in GSSL were transformed to 12 rare ginsenosides using glutamic acid as catalyst. • T-GSSL ameliorates metabolic disorders, lipid ectopic deposition, and obesity, and maintains glucose homeostasis in obese rats. • T-GSSL attenuates obesity through PKA/CREB pathway via REGγ negative regulation.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2024.11.005