Ganoderma lucidum Triterpenoids Suppress Adipogenesis and Obesity via PRKCQ Activation: An Integrated In Vivo, In Vitro, and Systems Pharmacology Study

<i>Ganoderma lucidum</i> triterpenoids (GLTs) exhibit potential anti-obesity activity. However, their mechanism remains unclear. In this study, triterpenoids were extracted from <i>G. lucidum</i> 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 <i>PPARγ</i>, <i>C/EBPα</i>, <i>FASN</i>, and <i>SCD-1.</i> Moreover, network pharmacology predicted a total of 306 potential targets, among which <i>FYN</i>, <i>PRKCQ</i>, <i>PTPRF</i>, <i>HRH1,</i> and <i>HCRTR2</i> 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.