Abstract
Ganoderma lucidum triterpenoids (GLTs) exhibit potential anti-obesity activity. However, their mechanism remains unclear. In this study, triterpenoids were extracted from G. lucidum via ultrahigh-pressure extraction. Using a high-fat diet (HFD)-induced mouse model, we showed that GLT treatment (100 and 200 mg/kg) significantly reduced body weight and lipid accumulation without changing food intake. Next, we found that GLT significantly inhibited preadipocyte differentiation and adipogenesis and reduced the expression of adipogenic genes, including PPARγ, C/EBPα, FASN, and SCD-1. Moreover, network pharmacology predicted a total of 306 potential targets, among which FYN, PRKCQ, PTPRF, HRH1, and HCRTR2 were identified as the core targets via a machine learning algorithm. Interestingly, GLT upregulated the expression of PRKCQ, while the deletion of PRKCQ significantly reversed the anti-adipogenic effect of GLT. In addition, we found that neutral GLT may play a dominant role in inhibiting adipogenic differentiation. These findings suggest for the first time that GLT inhibits adipogenesis and lipid accumulation via the induction of PRKCQ in adipocytes. This study provides a scientific basis for the application of GLT in the prevention and treatment of obesity, as both a pharmaceutical agent and a functional food.