Phosphatidylserine Ameliorates High-Fat Diet-Induced Obesity Through Modulating the Bile Acid Metabolism and Gut...

Obesity has emerged as a prevalent clinical and public health concern in contemporary society, imposing significant economic and social burdens worldwide. Phosphatidylserine (PS), a functionally diverse phospholipid, demonstrates multiple biological activities. This study delves into the efficacy and underlying mechanisms of PS in mitigating high-fat diet (HFD)-induced obesity in mice. Comprehensive physiological and biochemical assessments revealed that both preventive and therapeutic interventions with PS effectively attenuated lipid accumulation, liver dysfunction, and obesity associated with HFD consumption. Metabolomic analyses further illuminated that HFD mice hepatic cholic acid (CA), β-muricholic acid (β-MCA), and deoxycholic acid (DCA) contents were significantly decreased by 42.5%-58.5%, 66.4%-69.0%, and 11.0%-12.2%, respectively, after PS administration. And serum α-muricholic acid (α-MCA) and ω-muricholic acid (ω-MCA) were also significantly reduced by 19.2%-23.4% and 9.3%-11.5%, respectively. 16S rDNA sequencing highlighted the modulatory effects of PS on gut microbiota composition in HFD mice. Specifically, PS treatment positively correlated with the abundance of Alloprevotella and inversely correlated with Parasutterella, Olsenella, and Allobaculum, suggesting a targeted modulation of the gut microbial ecosystem. In summary, this study highlights the therapeutic potential of PS in mitigating HFD-induced obesity through modulation of bile acid metabolism and gut microbiota composition. These findings provide a scientific foundation for further exploration of PS as a viable nutraceutical or therapeutic agent in obesity intervention strategies.