Chronotoxicity of Acrylamide in Mice Fed a High-Fat Diet: The Involvement of Liver CYP2E1 Upregulation and Gut Leakage
Luanfeng Wang,
Yanhong Liu,
Huajing Gao,
Shuqi Ge,
Xinru Yao,
Chang Liu,
Xintong Tan
Affiliations
Luanfeng Wang
Collaborative Innovation Center for Modern Grain Circulation and Safety, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China
Yanhong Liu
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Huajing Gao
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Shuqi Ge
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Xinru Yao
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Chang Liu
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Xintong Tan
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
Acrylamide (ACR) is produced under high-temperature cooking of carbohydrate-rich foods via the Maillard reaction. It has been reported that ACR has hepatic toxicity and can induce liver circadian disorder. A high fat diet (HFD) could dysregulate liver detoxification. The current study showed that administration of ACR (100 mg/kg) reduced the survival rate in HFD-fed mice, which was more pronounced when treated during the night phase than during the day phase. Furthermore, ACR (25 mg/kg) treatment could cause chronotoxicity in mice fed a high-fat diet, manifested as more severe mitochondrial damage of liver during the night phase than during the day phase. Interestingly, HFD induced a higher CYP2E1 expressions for those treated during the night phase, leading to more severe DNA damage. Meanwhile, the expression of gut tight junction proteins also significantly decreases at night phase, leading to the leakage of LPSs and exacerbating the inflammatory response at night phase. These results indicated that a HFD could induce the chronotoxicity of ACR in mice liver, which may be associated with increases in CYP2E1 expression in the liver and gut leak during the night phase.
