Cordycepin Ameliorates High Fat Diet-Induced Obesity by Modulating Endogenous Metabolism and Gut Microbiota Dysbiosis

Background: Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. Methods: In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. Results: CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. Conclusions: According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.