Chlorogenic acid improves obesity by regulating serum metabolites

Obesity, a globally prevalent chronic metabolic disorder, has been increasingly confirmed to involve gut microbiota as a pivotal regulator in its pathogenesis. Chlorogenic acid (CGA) has been reported to exert beneficial effects on lipid metabolism regulation and obesity amelioration. However, the mechanisms by which CGA alleviates obesity via modulation of the intestinal microbiota remain unclear. We established a DIO mouse model by HFD induction, and combined untargeted serum metabolomics and FMT experiments to elucidate its effect and mechanism. Our results show that CGA ameliorates obesity-related metabolic phenotypes, suppresses HFD-induced intestinal inflammation, and enhances intestinal mucosal barrier integrity, which synergistically restore gut microbiota homeostasis. Integrative analysis of 16S rRNA gene high-throughput sequencing and serum untargeted metabolomics showed CGA modulates gut microbiota (downregulating Desulfovibrio and Allobaculum, upregulating Oscillospira), which alters serum metabolites (increasing linoleic acid, decreasing hexadecanoic and tetradecanoic acids). These effects inhibited hepatic lipid synthesis (e.g., FASN, ACACA, and SCD1 genes) and lipid uptake (e.g., FABP4, SCP2, and CD36 genes), thereby ameliorating obesity. Importantly, consistent results were also observed for interventions with fecal microbiota transplantation from CGA-treated mice. This finding confirms that the anti-obesity effect of CGA is closely associated with the modulation of gut microbiota.