Liu Shuang, Chen Xiaoling, Chen Daiwen, Yu Bing, Zheng Ping, Luo Yuheng, He Jun, Huang Zhiqing
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China.
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China.
J Nutr Biochem. 2025 Apr;138:109844. doi: 10.1016/j.jnutbio.2025.109844. Epub 2025 Jan 20.
Inhibition of appetite is an effective approach to fight obesity. Recently, bile acids have been reported to suppress appetite and alleviate obesity via the Takeda G protein-coupled receptor 5 (TGR5). However, whether the downstream signaling molecule cyclic adenosine monophosphate (cAMP) of TGR5 is involved in this process remains unclear. Oleanolic acid (OA) is a plant analogue of bile acids. The study aimed to explore the effect of dietary OA supplementation on appetite and to examine the role of TGR5/cAMP signaling in this process. In our study, mice were divided into four treatment groups: basal diet, 50mg/kg OA-supplemented diet, 100mg/kg OA-supplemented diet, and 30mg/kg tauroursodeoxycholic acid (TUDCA)-supplemented diet. Our results showed that dietary supplementation of OA and TUDCA both suppressed appetite. Additionally, OA and TUDCA downregulated the expression of appetite-stimulating factors while upregulating appetite-suppressing factors in the hypothalamus. Furthermore, OA was found to activate TGR5 signaling in the hypothalamus. Mechanistic studies using N38 cells revealed that OA reduced the expression and secretion of agouti-related peptide (AgRP), while inhibition of TGR5 and cAMP attenuated this effect of OA. In conclusion, our findings suggest that OA may suppress appetite through activation of the TGR5/cAMP signaling pathway in the hypothalamus.
抑制食欲是对抗肥胖的一种有效方法。最近，有报道称胆汁酸可通过武田G蛋白偶联受体5（TGR5）抑制食欲并减轻肥胖。然而，TGR5的下游信号分子环磷酸腺苷（cAMP）是否参与此过程仍不清楚。齐墩果酸（OA）是胆汁酸的一种植物类似物。该研究旨在探讨饮食中补充OA对食欲的影响，并研究TGR5/cAMP信号在此过程中的作用。在我们的研究中，小鼠被分为四个处理组：基础饮食组、补充50mg/kg OA的饮食组、补充100mg/kg OA的饮食组和补充30mg/kg牛磺熊去氧胆酸（TUDCA）的饮食组。我们的结果表明，饮食中补充OA和TUDCA均能抑制食欲。此外，OA和TUDCA下调了下丘脑食欲刺激因子的表达，同时上调了食欲抑制因子的表达。此外，发现OA可激活下丘脑的TGR5信号。使用N38细胞进行的机制研究表明，OA可降低刺鼠相关肽（AgRP）的表达和分泌，而抑制TGR5和cAMP可减弱OA的这种作用。总之，我们的研究结果表明，OA可能通过激活下丘脑的TGR5/cAMP信号通路来抑制食欲。
