AHR Deficiency Exacerbates Hepatic Cholesterol Accumulation via Inhibiting Bile Acid Synthesis in MAFLD Rats
文献类型：期刊论文
| 作者 | Xu, Junjiu1,6; Liu, Pengwei3,4,5; Wu, Yuling1,3; He, Hongxiu1,6; Hu, Dandan3; Sun, Jianhua3,6; Chen, Jing6; Tian, Ying3; Gong, Likun1,2,3,4,5,6 |
| 刊名 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
 |
| 出版日期 | 2025-12-29 |
| 卷号 | 27期号:1页码:19 |
| 关键词 | MAFLD AHR bile acid cholesterol gut microbiota |
| ISSN号 | 1661-6596 |
| DOI | 10.3390/ijms27010349 |
| 英文摘要 | Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by abnormal lipid metabolism. The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor involved in regulating multiple physiological processes. Recent studies have demonstrated that AHR exerts a multifaceted regulatory role in liver diseases by integrating metabolic and immune signaling pathways; however, the specific role of AHR in MAFLD is not clear. In our work, a rat model of MAFLD was established by feeding wild-type (WT) and AHR knockout (AHR-/-) rats with a high-fat, high-fructose, and high-cholesterol diet (HFHFrHCD) for 10 weeks, and then the liver injury markers, lipid-related biochemical indices and liver histopathology were examined to elucidate the effect of AHR on MAFLD progression. We discovered that AHR deficiency can elevate plasma transaminase levels, increase hepatic triglyceride (TG) and total cholesterol (TC), and exacerbate insulin resistance (IR) under an overnutrition environment. Subsequently, liver transcriptome and RT-qPCR were performed to investigate the underlying mechanism, which revealed that the hepatic bile acid synthesis was inhibited because of lower Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1) expression in the liver when AHR was knockout. Additionally, intestinal flora dysbiosis occurred in AHR-/- rats fed with HFHFrHCD, which might also contribute to the hepatic cholesterol accumulation. Taken together, our results suggested that AHR might play an important role in regulating cholesterol metabolism by inhibiting bile acid synthesis and breaking the steady state of the gut microbiota during the MAFLD progression. |
| WOS关键词 | CLINICAL CHARACTERISTICS ; LIVER ; OUTCOMES ; DISEASE ; NAFLD ; NASH ; MICE |
| 资助项目 | High-level Innovative Research Institute of the Department of Science and Technology of Guangdong Province[2021B0909050003] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001657439600001 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322542]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Tian, Ying; Gong, Likun |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, China Serbia Belt & Rd Joint Lab Nat Prod & Drug D, 555 Zu Chong Zhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 4.Guizhou Med Univ, Sch Pharmaceut Sci, Guiyang 561113, Guizhou, Peoples R China 5.Guizhou Med Univ, State Key Lab Discovery & Utilizat Funct Component, Guiyang 561113, Guizhou, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Junjiu,Liu, Pengwei,Wu, Yuling,et al. AHR Deficiency Exacerbates Hepatic Cholesterol Accumulation via Inhibiting Bile Acid Synthesis in MAFLD Rats[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2025,27(1):19. |
| APA | Xu, Junjiu.,Liu, Pengwei.,Wu, Yuling.,He, Hongxiu.,Hu, Dandan.,...&Gong, Likun.(2025).AHR Deficiency Exacerbates Hepatic Cholesterol Accumulation via Inhibiting Bile Acid Synthesis in MAFLD Rats.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,27(1),19. |
| MLA | Xu, Junjiu,et al."AHR Deficiency Exacerbates Hepatic Cholesterol Accumulation via Inhibiting Bile Acid Synthesis in MAFLD Rats".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 27.1(2025):19. |
入库方式： OAI收割
来源：上海药物研究所
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