Exogenous natural EPA-enriched phosphatidylcholine and phosphatidylethanolamine ameliorate lipid accumulation and insulin resistance via activation of PPARα/γ in mice

Nuclear receptor peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of glucose homeostasis and lipid metabolism. Here, in a protein-lipid overlay assay, we show that EPA-enriched phosphatidylcholine (EPA-PC) and phosphatidylethanolamine (EPA-PE), isolated from sea cucumber, bind to PPAR alpha/PPAR gamma. An established dual-luciferase reporter gene assay system in NIH3T3 cells showed the exert agonistic activity of EPA-PC and EPA-PE with respect to the transcription of PPAR alpha and PPAR gamma. The treatments of EPA-PC and EPA-PE induced PPAR alpha-mediated fatty acid oxidation in mouse hepatocytes and liver. In a preadipocytes differentiation assay, EPA-PC and EPA-PE promoted the differentiation of preadipocytes to differentiated adipocytes and upregulated the expression of lipid metabolic target genes of the PPAR gamma and inhibited the phosphorylation of PPAR gamma at Ser273. We further examined the effects of EPA-PC and EPA-PE on high-fat high-sucrose diet (HFSD) induced insulin resistance and found that insulin resistance as well as abnormal lipid accumulation was ameliorated by EPA-PC and EPA-PE.