Chlorogenic Acid Ameliorates Lipid Metabolism Disorders via Gut Microbiota‐Serum Metabolite‐Liver Axis in High‐Fat Diet‐Induced Obesity

Obesity is a global metabolic disorder in which gut microbiota has emerged as a pivotal regulator. Chlorogenic acid (CGA) has been reported to improve lipid metabolism and mitigate obesity; however, its microbiota-mediated mechanisms remain unclear. Here, we established a diet-induced obesity (DIO) mouse model by high-fat diet feeding and integrated serum metabolomics, liver transcriptomics, and fecal microbiota transplantation (FMT) to elucidate the effects of CGA. CGA supplementation alleviated obesity-related phenotypes, reduced intestinal inflammation, and preserved mucosal barrier integrity, thereby restoring microbial homeostasis. Combined 16S rRNA sequencing and untargeted metabolomics revealed that CGA reshaped gut microbiota (suppressing Desulfovibrio and Allobaculum, enriching Oscillospira), accompanied by altered serum metabolites (elevated linoleic acid, reduced hexadecanoic and tetradecanoic acids). Transcriptomic analysis demonstrated that CGA downregulated genes related to hepatic lipid synthesis (FASN, ACACA, SCD1) and lipid uptake (FABP4, SCP2, CD36), which was further validated by qRT-PCR. Importantly, FMT from CGA-treated mice reproduced the metabolic improvements, confirming that the beneficial effects of CGA are closely associated with gut microbiota modulation. Collectively, these findings indicate that CGA ameliorates obesity through modulation of the gut microbiota-serum metabolite-liver axis.