The exogenous natural phospholipids, EPA-PC and EPA-PE, contributes to
ameliorate lipid accumulation and inflammation via activation of PPARα/γ
Background and Purpose: PPARα/γ play an important role in glucose
homeostasis and lipid metabolism making it an attractive anti‐diabetic
target. Focusing on the development of PPARα/γ dual agonists, we
evaluated the activity of phosphatidylcholine (EPA-PC) and
phosphatidylethanolamine (EPA-PE) on PPARα/γ. Moreover, we investigated
the long‐term effects of EPA-PC and EPA-PE on insulin resistance.
Experimental Approach: The activities of EPA-PC/PE with respect PPARα/γ
transcription were tested using a luciferase reporter gene assay, lipid
binding assay and a Protein-Lipid overlay assay. Moreover, the agonistic
effects of EPA-PC/PE on PPARα/γ were evaluated in HepG2 and 3T3L1.
respectively. In a 3T3L1/Raw264.7 transwell system, the effect of
EPA-PC/PE on macrophages polarization and inflammation were studied. In
mice, we sought to determine if insulin resistance and lipid
accumulation induced by high-fat high-sucrose diet, was attenuated by
EPA-PC or EPA-PE diet (0.3% of diet). Key Results: EPA-PC/PE are potent
PPARα/γ dual agonists, which promoted hepatic PPARα-mediated fatty acid
oxidatio, and promoted the preadipocytes differentiation and PPARγ
target genes expression in adipocytes. In mice on the HFSD, EPA-PC/PE
significantly suppressed body weight gain and ameliorated insulin
resistance as well as abnormal glucose and lipid metabolism. EPA-PC/PE
could regulate PPARγ-responsive genes and slightly inhibited the
phosphorylation of PPARγ at Ser273, resulted in adipose tissue
remodeling. Finally, we found that EPA-PC/PE promoted macrophages
polarization and attenuated inflammation in vitro and in vivo.
Conclusion and Implications: These data indicate that the exogenous
natural phospholipids, EPA-PC or EPA-PE, activate PPARα/γ, may be useful
for the treatment of insulin resistance.