Emerging evidence suggests that sea cucumber ether phospholipids (ether-PLs) can modulate high-fat diet (HFD)-induced metabolic disorders. However, whether this modulation is associated with metabolic pathways related to oxidative stress and inflammation remains unclear. This study aimed to investigate the antioxidative and anti-inflammatory effects on HFD-fed mice and the associated metabolism pathways in response to administration with sea cucumber ether-PLs using integrated biochemistry and a metabolomics approach. Biochemistry analysis and histological examinations showed that sea cucumber ether-PLs significantly decreased body weight gain and fat deposition in tissues. PE-P was superior to PC-O in alleviating reactive oxygen species (ROS), malondialdehyde (MDA) and inflammatory responses (IL-6, TNF-α and MCP-1) in the HFD-induced mouse model. Serum metabolomics analysis revealed that it upregulated four metabolites and downregulated twenty-four metabolites compared to those in HFD mice after ether-PL administration. Pathway analysis indicated that sea cucumber ether-PLs alleviate the HFD-induced inflammation and oxidative stress by three main...

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