Effect of di (2-ethylhexyl) phthalat on hepatic lipid metabolism in mice by Notch

• 1、Guangdong University of Technology, School of Biomedical and Pharmaceutical Sciences, Guangzhou 510006

Abstract：Objective: To investigate the mechanism of Notch signaling pathway in hepatic lipid metabolism in mice caused by di (2-ethylhexyl) phthalate, and reveal the effects of HFD on the toxicity of DEHP. Methods: 6-week-old C57BL/6J male mice were fed a normal diet (ND) and a high-fat diet (HFD). After 4 weeks of dietary intervention, ND and HFD mice were exposed to 0, 0.073mg/kg/d and 7.3 mg/kg/d DEHP for 10 weeks, respectively. The physiological parameters of mice were observed; H&E staining was performed on the liver of mice exposed to DEHP. Notch pathway related genes and liver lipid metabolism genes were detected by RT-qPCR assay after DEHP exposure. Human normal hepatocyte (L02) inhibition assay was used to verify the role of Notch pathway in mouse hepatic lipid metabolism. Results: DEHP exposure led to the activation of Notch pathway in normal mice liver, increased fat synthesis and decreased lipolysis, which resulted in lipid accumulation, weight gain, dyslipidemia and inflammatory response. DEHP exposure led to the activation of Notch pathway in the liver of obese mice, increased fat synthesis and lipolysis, which resulted in more serious lipid metabolism disorder and significant liver injury, but caused no significant changes in body weigh. The lipid accumulation and inflammatory response in L02 cells induced by DEHP was alleviated after inhibiting Notch-1. Conclusion: DEHP exposure induces abnormal hepatic lipid metabolism and inflammation in mice through Notch signaling pathway, and obesity may have a joint effect with DEHP on hepatic lipid metabolism disorder.

Keywords： Di (2-ethylhexyl) phthalate obesity Notch hepatic lipid metabolism