2. Academic Validation
  3. 1,3-dichloro-2-propanol caused lipid droplets accumulation by suppressing neutral lipases via BMAL1 in hepatocytes

1,3-dichloro-2-propanol caused lipid droplets accumulation by suppressing neutral lipases via BMAL1 in hepatocytes

  • Food Chem Toxicol. 2023 Feb 17;113670. doi: 10.1016/j.fct.2023.113670.
Yong Fan 1,  Jing Lu 2,  Jinghui Fan 3,  Shuang Guan 4
Affiliations

Affiliations

  • 1 College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
  • 2 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.
  • 3 Department of Pharmacy, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, 157011, People's Republic of China.
  • 4 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. Electronic address: [email protected].
PMID: 36805544 DOI: 10.1016/j.fct.2023.113670
Abstract

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. 1box. 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.

Keywords

1,3-dichloro-2-propanol; Circadian rhythm; Lipid droplets; Neutral lipases.

Figures
Products