Oleanolic acid inhibits appetite through the TGR5/cAMP signaling pathway

Abstract

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.