Chlorogenic acid inhibits intestinal lipid uptake and promotes adipose lipid catabolism via epithelium-derived exosomes in ob/ob mice.

Chlorogenic acid has been widely reported to regulate lipid metabolism and alleviate obesity; however, its effects on intestinal lipid uptake and adipose tissue catabolism, as well as the underlying mechanisms, remain incompletely understood. In the present study, diabetic ob/ob mice were treated with chlorogenic acid, which significantly improved metabolic parameters, including body weight, serum triglyceride levels, glucose tolerance, and insulin sensitivity. Notably, chlorogenic acid reduced intestinal lipid content and downregulated the expression of genes involved in lipid transportation. Concurrently, epididymal adipose tissue weight was decreased, accompanied by enhanced expression of genes associated with lipid catabolism. Mechanistically, chlorogenic acid decreased triglyceride level and suppressed PPARγ protein expression in IPEC-J2 cells. Activation of PPARγ attenuated the inhibitory effects of chlorogenic acid on lipid accumulation, indicating a critical role of PPARγ signaling. In addition, chlorogenic acid altered the concentration of epithelial cell-derived exosomes. These exosomes reduced triglyceride levels and modulated the expression of lipid metabolism-related genes in 3T3-L1 cells. Collectively, our findings suggest that chlorogenic acid may exert metabolic benefits, at least in part, through a coordinated intestine-adipose axis and provide preliminary evidence supporting a potential role for exosome-mediated inter-organ communication in the regulation of lipid homeostasis.