Lycopene Prevents DEHP-Induced Liver Lipid Metabolism Disorder by Inhibiting the HIF-1α-Induced PPARα/PPARγ/FXR/LXR System.
Yi ZhaoDe-Xing MaHong-Guang WangMu-Zi LiMilton TalukderHao-Ran WangJin-Long LiPublished in: Journal of agricultural and food chemistry (2020)
Di(2-ethylhexyl) phthalate (DEHP) is a widespread pollutant that badly affects animals and human health. Lycopene (LYC) has been used as a dietary supplement that has effective antioxidant and antiobesity functions. The present goal was to understand the molecular mechanisms of LYC preventing DEHP-induced lipid metabolism of the liver. The mice were intragastrically administered with LYC (5 mg/kg) and/or DEHP (500 mg/kg or 1000 mg/kg). Here, we found that LYC attenuated DEHP-caused hepatic histopathological lesions including steatosis. Hematological and biochemical analyses revealed that LYC ameliorated DEHP-caused liver function and lipid metabolism disorders. DEHP caused lipid metabolism disorders via activating the peroxisome proliferator activated receptor α/γ (PPARα/γ) signal transducer and Farnesoid X receptor (FXR)/liver X receptor (LXR) signaling pathway. As a major regulator of lipid metabolism, hypoxia-inducible factor-1α (HIF-1α) system was elevated with increased fatty degeneration under DEHP exposure. However, LYC could decrease the levels of HIF-1α/PPARα/PPARγ/FXR/LXR signaling pathway-related factors. Our research indicated that LYC could prevent DEHP-induced lipid metabolism disorders via inhibiting the HIF-1α-mediated PPARα/PPARγ/FXR/LXR system. This study may provide a possible molecular mechanism for fatty liver induced by DEHP.
Keyphrases
- signaling pathway
- fatty acid
- insulin resistance
- high glucose
- diabetic rats
- endothelial cells
- human health
- risk assessment
- oxidative stress
- pi k akt
- epithelial mesenchymal transition
- drug induced
- high fat diet induced
- type diabetes
- skeletal muscle
- metabolic syndrome
- high fat diet
- pseudomonas aeruginosa
- cell proliferation
- induced apoptosis
- anti inflammatory
- endoplasmic reticulum stress