miR-18a-5p/PXR/SREBP2 Was Involved in MAFLD Associated With Methyl Tert-Butyl Ether Among Petrol Station Workers

  • Liver Int. 2025 Feb;45(2):e16246. doi: 10.1111/liv.16246.
Hanyun Wang  1 ,  Mingxiao Guo  1 ,  Fengtao Cui  1  2 ,  Mengdi Li  3 ,  Xianan Zhang  4 ,  Wei Gao  2 ,  Xingqiang Fang  2 ,  Li Chen  1 ,  Ye Xin  1 ,  Yucheng Sun  1 ,  Piye Niu  1 ,  Junxiang Ma  1
Affiliations
  • 1. Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.
  • 2. Occupational Disease Prevention and Control Hospital of Huaibei Mining Co. Ltd., Huaibei, Anhui Province, China.
  • 3. Institute for Occupational Health, Beijing Center for Diseases Control and Prevention, Beijing, China.
  • 4. Yanjing Medical College, Capital Medical University, Beijing, China.
PMID: 39821525 DOI: 10.1111/liv.16246
Abstract

Background: Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.

Methods: We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.

Results: Blood MTBE levels were found to be significantly correlated with an increased risk of MAFLD, and MAFLD risk increased by 24.3% for every 0.1 μg/L increase in blood MTBE. Consistently, we found that MTBE exposure could induce MAFLD in rats and HepaRG cells, and activate pregnane X receptor (PXR) by inhibiting miR-18a-5p to upregulate the expression of sterol regulatory element-binding protein 2 (SREBP2) and its nuclear translocation, thereby upregulating the expression of its downstream target genes.

Conclusions: Our study demonstrated that MTBE exposure might be a significant risk factor for MAFLD, and MTBE could promote liver Cholesterol synthesis and lipid deposition by activating the miRNA-18a-5p/PXR/SREBP2 pathway.

Keywords
MAFLD; Pregnane X receptor (PXR); methyl tert‐butyl ether (MTBE); miRNA‐18a‐5p; sterol regulatory element‐binding protein 2 (SREBP2).
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