Integrating untargeted and oxylipins-targeted metabolomics to reveal the anti-obesity and hypolipidemic mechanism of conjugated linoleic acid in high-fat diet rats

This study aimed to investigate the metabolites of conjugated linoleic acid (CLA) in vivo from the perspective of metabolomics, so as to reveal the potential mechanism of CLA in lowing blood lipids. 30 male non-adult SD rats were divided into: normal diet group, high-fat diet group, and CLA group (intragastric administration of 0.5 g/kg·BW CLA). Results indicate improvements in body weight and visceral fat deposition in obese rats treated with CLA. Metabolomic analysis reveals significant changes in the arachidonic acid (ARA) pathway and its intestinal metabolite oxylipins. Key biomarkers (PGE1, PGE2, TXB2, PGF2α, and 12S-HHTrE) catalyzed by Cox and Lox are identified, influencing blood lipid reduction. Network analysis links these biomarkers to Pparγ. PCR and western blot confirm Pparγ changes in rat liver and intestine, impacting downstream lipid metabolism. This study reveals a potential mechanism: CLA mitigates obesity through the ARA-Cox/Lox-PGE2-Pparγ pathway, offering insights for treating obesity and dyslipidemia.