Fan Yong, Lu Jing, Fan Jinghui, Guan Shuang
College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China; Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
Food Chem Toxicol. 2023 Apr;174:113670. doi: 10.1016/j.fct.2023.113670. Epub 2023 Feb 18.
Circadian rhythm regulates body physiology and metabolism to adapt to the external environment. 1,3-dichloro-2-propanol (1,3-DCP) is a food pollutant formed during food processing. Our study explored whether toxicity of 1,3-DCP was related to circadian rhythm. We discovered that 1,3-DCP caused lipid droplets (LDs) accumulation via suppression of neutral lipases ATGL and HSL in mice liver and HepG2 cells. Meanwhile, 1,3-DCP caused rhythmic disruption of key circadian rhythm molecules BMAL1/CLOCK at protein and mRNA levels in HepG2 cells. Studies have shown that BMAL1 regulates PPARα by binding to the promoter E-box. 1,3-DCP inhibited PPARα expression. A PPARα activator WY-14643 up-regulated ATGL and HSL expression. BMAL1 overexpression up-regulated PPARα, ATGL and HSL expression. WY-14643 or BMAL1 overexpression attenuated 1,3-DCP-caused LDs accumulation in HepG2 cells. The results revealed that 1,3-DCP caused LDs accumulation by neutral lipases suppression via inhibiting key circadian rhythm protein BMAL1, indicating that circadian rhythm can be related to the regulation of LDs accumulation caused by 1,3-DCP.
昼夜节律调节身体生理和新陈代谢以适应外部环境。1,3 - 二氯 - 2 - 丙醇（1,3 - DCP）是食品加工过程中形成的一种食品污染物。我们的研究探讨了1,3 - DCP的毒性是否与昼夜节律有关。我们发现，1,3 - DCP通过抑制小鼠肝脏和HepG2细胞中的中性脂肪酶ATGL和HSL导致脂滴（LDs）积累。同时，1,3 - DCP在蛋白质和mRNA水平上导致HepG2细胞中关键昼夜节律分子BMAL1/CLOCK的节律紊乱。研究表明，BMAL1通过与启动子E - 盒结合来调节PPARα。1,3 - DCP抑制PPARα表达。一种PPARα激活剂WY - 14643上调ATGL和HSL表达。BMAL1过表达上调PPARα、ATGL和HSL表达。WY - 14643或BMAL1过表达减弱了1,3 - DCP在HepG2细胞中引起的LDs积累。结果表明，1,3 - DCP通过抑制关键昼夜节律蛋白BMAL1导致中性脂肪酶抑制从而引起LDs积累，这表明昼夜节律可能与1,3 - DCP引起的LDs积累的调节有关。
