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

## TL;DR

This study shows that compounds from Ganoderma lucidum reduce obesity by activating PRKCQ, offering a new approach for obesity prevention and treatment.

## Contribution

The study identifies PRKCQ as a novel target for GLT's anti-obesity effects through integrated experimental and computational methods.

## Key findings

- GLT reduced body weight and lipid accumulation in mice without affecting food intake.
- GLT inhibited adipogenesis and downregulated key adipogenic genes like PPARγ and C/EBPα.
- PRKCQ activation was crucial for GLT's anti-adipogenic effects, as its deletion reversed these effects.

## 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.