Ameliorative potential of ellagic acid via PPARγ against hyperlipidemia: Insights from mice and zebrafish

ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) was a major transcription factor and performed an essential function in the regulation of lipid metabolism. Ellagic acid (EA) was a natural phytochemical extracted from berries and pomegranates, and research had demonstrated its ameliorative effects on lipid metabolism disorders. We intended to explore the interventional effect and mechanism of action of EA on hyperlipidemia. In vitro experiments revealed that EA could reduce lipid accumulation in HepG2 cells. EA was found to bind stably to PPARγ, suppressing its nuclear translocation as well as its luciferase activity. It could also down-regulate the expression of genes and proteins related to lipid metabolism upstream and downstream of PPARγ. To explore the impact of EA on hyperlipidemia in vivo from different levels and perspectives, we established hyperlipidemia mice and hyperlipidemia zebrafish models. Consistent with the in vitro results, in vivo experiments revealed that EA attenuated lipid accumulation in hyperlipidemia mice and reduced the levels of related inflammatory factors in their serum. EA also inhibited lipid accumulation by decreasing the expression of upstream and downstream lipid-associated genes of pparg in hyperlipidemia zebrafish. In conclusion, EA could effectively improve hyperlipidemia by regulating PPARγ.