Curcumol effectively improves obesity through GDF15 induction via activation of endoplasmic reticulum stress response

The escalating prevalence of obesity presents a formidable global health challenge, underscoring the imperative for efficacious pharmacotherapeutic interventions. However, current anti-obesity medications often exhibit limited efficacy and adverse effects, necessitating the exploration of alternative therapeutic approaches. Growth differentiation factor 15 (GDF15) has emerged as a promising target for obesity management, given its crucial role in appetite control and metabolic regulation. In this study, we aimed to investigate the efficacy of curcumol, a sesquiterpene compound derived from plants of the Zingiberaceae family, in obesity treatment. Our findings demonstrate that curcumol effectively induces the expression of GDF15 through the activation of the endoplasmic reticulum stress pathway. To confirm the role of GDF15 as a critical target for curcumol's function, we compared the effects of curcumol in wild-type mice and Gdf15-knockout mice. Using a high-fat diet-induced obese murine model, we observed that curcumol led to reduced appetite and altered dietary preferences mediated by GDF15. Furthermore, chronic curcumol intervention resulted in promising anti-obesity effects. Additionally, curcumol administration improved glucose tolerance and lipid metabolism in the obese mice. These findings highlight the potential of curcumol as a GDF15 inducer and suggest innovative strategies for managing obesity and its associated metabolic disorders. In conclusion, our study provides evidence for the efficacy of curcumol in obesity treatment by inducing GDF15 expression. The identified effects of curcumol on appetite regulation, dietary preferences, glucose tolerance, and lipid metabolism emphasize its potential as a therapeutic agent for combating obesity and related metabolic disorders.