2. Academic Validation
  3. A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F

  • J Biomed Res. 2024 Feb 23;38(5):451-463. doi: 10.7555/JBR.37.20230169.
Jing Xue 1 2,  Linwei Zhang 1,  Jingxian Tao 1,  Xuexue Xie 1,  Xi Wang 1,  Linlin Wu 3,  Shuhu Du 4,  Ninghua Tan 5,  Yang Jin 6,  Jianming Ju 7,  Junting Fan 5 6,  Jun Wang 1,  Fei Huan 1,  Rong Gao 8
Affiliations

Affiliations

  • 1 Key Laboratory of Modern Toxicology, Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 2 Taizhou Center for Disease Control and Prevention, Taizhou, Jiangsu 225300, China.
  • 3 Wuxi Center for Disease Control and Prevention, Wuxi, Jiangsu 214023, China.
  • 4 School of Pharmacy, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 5 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 6 Department of Pharmaceutical Analysis, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 7 Laboratory of Quality and Metabolomics of Traditional Chinese Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, China.
  • 8 Department of Hygienic Analysis and Detection, Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
PMID: 38808572 DOI: 10.7555/JBR.37.20230169
Abstract

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including Acetyl-CoA Carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, Peroxisome Proliferator-activated Receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both in vitro and in vivo studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from Swertia chirayita, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

Keywords

bellidifolin; bisphenol F; lipogenesis; non-alcoholic fatty liver disease.

Figures
Products