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Mechanism by which benzo[a]pyrene activates AhR to regulate FGF-21 and affect lipid metabolism in HepG2 cells
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Xue WANG1, 2, Lei FAN1, 2, Yu-lu DU1, 2, Wei-zhong HUANGFU1, 3, Meng-di ZHANG1, 2, Xiao-li LÜ1, 2, Yu-xia HU1, 2, Jun LI1, 2, Shu-hong ZHOU1, 2, Tu-ya BAI1, 2, *, Fu-hou CHANG1, 2, *
Acta Pharmaceutica Sinica | 2026, 61(9) : 3424 - 3432
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Acta Pharmaceutica Sinica | 2026, 61(9): 3424-3432
• Original Articles •
Mechanism by which benzo[a]pyrene activates AhR to regulate FGF-21 and affect lipid metabolism in HepG2 cells
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Xue WANG1, 2, Lei FAN1, 2, Yu-lu DU1, 2, Wei-zhong HUANGFU1, 3, Meng-di ZHANG1, 2, Xiao-li LÜ1, 2, Yu-xia HU1, 2, Jun LI1, 2, Shu-hong ZHOU1, 2, Tu-ya BAI1, 2, *, Fu-hou CHANG1, 2, *
Affiliations
  • 1College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
  • 2The Engineering Research Center for New Drug Screening of Inner Mongolia Autonomous Region, Hohhot 010110, China
  • 3The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010110, China
Published: 2026-09-12 doi: 10.16438/j.0513-4870.2026-0148
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This study investigated the effects of different doses of benzo[a]pyrene (BaP) on the expression of fibroblast growth factor 21 (FGF-21), lipid metabolism, and related genes in HepG2 cells, as well as whether these effects are mediated by the aryl hydrocarbon receptor (AhR). HepG2 cells were treated with 15, 30, and 60 μmol·L-1 BaP for 24 h. The levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in HepG2 cells were measured. The mRNA and protein expression levels of FGF-21, β-oxidation-related genes [peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1α (CPT-1α), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α)], and lipid synthesis-related genes [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and stearoyl-CoA desaturase 1 (SCD1)] were detected by qPCR and Western blot. A stable cell line with AhR silencing was established via lentiviral transduction, and the cells were treated with 30 μmol·L-1 BaP. Lipid content was assessed by oil red O staining, and the mRNA and protein expression levels of FGF-21, β-oxidation-related genes, and lipid synthesis-related genes were measured. Compared with the control group, all three doses of BaP (15, 30, and 60 μmol·L-1) increased the levels of TC, TG, and LDL-C in HepG2 cells. Compared with the 30 μmol·L-1 BaP group, the 60 μmol·L-1 BaP group showed higher levels of TC, TG, and LDL-C, lower mRNA and protein expression of FGF-21 and β-oxidation-related genes, and higher mRNA and protein expression of lipid synthesis-related genes. Following AhR silencing and treatment with 30 μmol·L-1 BaP, lipid content, as well as the levels of TC, TG, and LDL-C, decreased in HepG2 cells, and the mRNA and protein expression levels of FGF-21, β-oxidation-related genes, and lipid synthesis-related genes were all reduced. Different doses of BaP increased lipid content in HepG2 cells. However, low-dose BaP activated AhR, thereby relatively increasing FGF-21 expression, reducing lipid synthesis, and enhancing fatty acid β-oxidation. In contrast, high-dose BaP activated AhR but relatively decreased FGF-21 expression, increased lipid synthesis, and reduced fatty acid β-oxidation. The effects of BaP on FGF-21, lipid metabolism, and related genes are all mediated by AhR.

benzo[a]pyrene  /  aryl hydrocarbon receptor  /  fibroblast growth factor 21  /  lentiviral transfection  /  lipid metabolism
王雪, 范蕾, 杜雨露, 皇甫卫忠, 张梦迪, 吕晓丽, 胡玉霞, 李君, 周树宏, 白图雅, 常福厚. BaP激活AhR调控FGF-21影响HepG2细胞脂质代谢的机制. 药学学报, 2026 , 61 (9) : 3424 -3432 . DOI: 10.16438/j.0513-4870.2026-0148
Xue WANG, Lei FAN, Yu-lu DU, Wei-zhong HUANGFU, Meng-di ZHANG, Xiao-li LÜ, Yu-xia HU, Jun LI, Shu-hong ZHOU, Tu-ya BAI, Fu-hou CHANG. Mechanism by which benzo[a]pyrene activates AhR to regulate FGF-21 and affect lipid metabolism in HepG2 cells[J]. Acta Pharmaceutica Sinica, 2026 , 61 (9) : 3424 -3432 . DOI: 10.16438/j.0513-4870.2026-0148
Year 2026 volume 61 Issue 9
104
46
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Article Info
doi: 10.16438/j.0513-4870.2026-0148
  • Receive Date:2026-02-03
  • Online Date:2026-10-22
  • Published:2026-09-12
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  • Received:2026-02-03
  • Revised:2026-04-21
Affiliations
    1College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
    2The Engineering Research Center for New Drug Screening of Inner Mongolia Autonomous Region, Hohhot 010110, China
    3The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010110, China
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表12种不同金属材料的力学参数
科
Family
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Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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