Chen Jianbo, Sha Jiyue, Huo Xiaohui, Li Zhiman, Qu Di, Li Xueqing, Li Meijia
Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China.
J Ginseng Res. 2025 Mar;49(2):156-165. doi: 10.1016/j.jgr.2024.11.005. Epub 2024 Nov 28.
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 (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 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.
白色脂肪组织（WAT）褐变可促进产热，可能是治疗肥胖症的一个有前景的靶点。从人参茎叶转化而来的稀有皂苷（T-GSSL）具有多种生物学活性。然而，其潜在的抗肥胖作用及潜在机制仍 largely 未知。
选择五种氨基酸作为将人参皂苷转化为稀有皂苷的催化剂。通过给小鼠喂食高脂饮食（HFD）14 周建立肥胖小鼠模型。通过测量体重、脂肪量、能量消耗（EE）和葡萄糖耐量来评估 T-GSSL 对肥胖小鼠的影响。将 3T3-L1 细胞分化为成熟脂肪细胞并与 T-GSSL 一起孵育。采用免疫组织化学、免疫共沉淀（Co-IP）、酶联免疫吸附测定（ELISA）、蛋白质印迹（WB）、实时聚合酶链反应（PCR）等方法研究 T-GSSL 的作用靶点和作用机制。
以谷氨酸为催化剂水解 GSSL 中的人参皂苷，产生了 12 种稀有皂苷，总转化率为 95%。T-GSSL 改善了肥胖小鼠的代谢紊乱、脂质异位沉积和肥胖，并维持了葡萄糖稳态。T-GSSL 处理促进了高脂饮食小鼠和 3T3-L1 细胞中的脂肪褐变并增强了 EE。在用蛋白激酶 A（PKA）拮抗剂处理的细胞中或在进行 敲低时这些作用减弱，而在 REGγ 小鼠中则增强。抑制 REGγ 并同时激活 PKA/CREB 途径阐明了 T-GSSL 通过促进脂肪组织褐变来逆转肥胖的机制。
T-GSSL 通过抑制 REGγ 并随后激活 PKA/CREB 途径促进脂肪褐变，从而减轻饮食诱导的肥胖。
