Antrodia cinnamomea Extract Attenuates Obesity by Targeting Adipogenic Pathways and Gut Dysbiosis in High-Fat Diet-Fed Mice

Obesity is a major metabolic disorder driven by excessive adipogenesis and lipid accumulation. This study investigated the anti-obesity effects and molecular mechanisms of <i>Antrodia cinnamomea</i> alcohol extract (ACE) in 3T3-L1 preadipocytes and a high-fat diet (HFD)-induced obesity mouse model. In vitro, <i>Antrodia cinnamomea</i> alcohol extract significantly inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells by downregulating PPARγ and C/EBPα, while activating the AMPK pathway and suppressing MAPK signaling. In vivo, <i>Antrodia cinnamomea</i> alcohol extract administration reduced body weight, adipose tissue mass, and liver lipid accumulation in high-fat diet-fed mice, ameliorating non-alcoholic fatty liver disease (NAFLD) symptoms. Transcriptomic analysis of adipose tissue revealed that <i>Antrodia cinnamomea</i> alcohol extract modulated key gene expression profiles related to fatty acid metabolism and adipogenesis, suppressing lipid synthesis while enhancing β-oxidation. Furthermore, <i>Antrodia cinnamomea</i> alcohol extract rebalanced gut microbiota, increasing beneficial bacterial populations such as <i>Akkermansia</i> and <i>Bifidobacterium</i>, while reducing pro-inflammatory <i>Escherichia-Shigella</i> species. These findings demonstrate that <i>Antrodia cinnamomea</i> alcohol extract exerts multifaceted anti-obesity effects by regulating lipid metabolism, adipogenesis pathways, and gut microbiota composition, highlighting its potential as a natural therapeutic agent for obesity management.