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Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor

Authors :
Wei Lou
Meng-di Zhang
Qi Chen
Tu-Ya Bai
Yu-Xia Hu
Feng Gao
Jun Li
Xiao-Li Lv
Qian Zhang
Fu-Hou Chang
Source :
Lipids in Health and Disease, Vol 21, Iss 1, Pp 1-12 (2022)
Publication Year :
2022
Publisher :
BMC, 2022.

Abstract

Abstract Background Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. Methods (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. Results (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. Conclusion BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

Details

Language :
English
ISSN :
1476511X
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Lipids in Health and Disease
Publication Type :
Academic Journal
Accession number :
edsdoj.6b6b4a0dba984685b11aa91163096bdb
Document Type :
article
Full Text :
https://doi.org/10.1186/s12944-022-01627-9