• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

甲酰肽受体 2 决定非酒精性脂肪性肝病和脂肪性肝炎进展的性别特异性差异。

Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.

机构信息

Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea.

Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea.

出版信息

Nat Commun. 2022 Jan 31;13(1):578. doi: 10.1038/s41467-022-28138-6.

DOI:10.1038/s41467-022-28138-6
PMID:35102146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8803937/
Abstract

Nonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex affects NAFLD/NASH pathophysiology. Formyl peptide receptor 2 (FPR2) modulates inflammatory responses in several organs; however, its role in the liver is unknown. Here we show that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH. NASH-like liver injury was induced in both sexes during choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) feeding, but compared with females, male mice had more severe hepatic damage. Fpr2 was more highly expressed in hepatocytes and healthy livers from females than males, and FPR2 deletion exacerbated liver damage in CDAHFD-fed female mice. Estradiol induced Fpr2 expression, which protected hepatocytes and the liver from damage. In conclusion, our results demonstrate that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH, suggesting a novel therapeutic target for NAFLD/NASH.

摘要

非酒精性脂肪性肝病（NAFLD）是全球范围内一个重要的健康关注点，可进展为非酒精性脂肪性肝炎（NASH）。尽管男性的 NAFLD/NASH 患病率和严重程度高于绝经前女性，但性别如何影响 NAFLD/NASH 病理生理学仍不清楚。甲酰肽受体 2（FPR2）调节多个器官的炎症反应；然而，其在肝脏中的作用尚不清楚。在这里，我们显示 FPR2 介导了饮食诱导的 NAFLD/NASH 的性别特异性反应。在胆碱缺乏、L-氨基酸定义的高脂肪饮食（CDAHFD）喂养期间，男女均诱导出 NASH 样肝损伤，但与女性相比，雄性小鼠的肝损伤更严重。Fpr2 在雌性而非雄性的肝细胞和健康肝脏中的表达更高，FPR2 缺失加剧了 CDAHFD 喂养的雌性小鼠的肝损伤。雌二醇诱导 Fpr2 表达，从而保护肝细胞和肝脏免受损伤。总之，我们的结果表明，FPR2 介导了饮食诱导的 NAFLD/NASH 的性别特异性反应，这为 NAFLD/NASH 提供了一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/75831edaf92e/41467_2022_28138_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/b5dd3e19b47f/41467_2022_28138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/5a2117af744e/41467_2022_28138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/f29633aea334/41467_2022_28138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/d27065c3dcbc/41467_2022_28138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/9aec71cfa6ee/41467_2022_28138_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/664217e4d280/41467_2022_28138_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/926154d9e93f/41467_2022_28138_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/cb09a79a16a9/41467_2022_28138_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/c2d4d984919a/41467_2022_28138_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/75831edaf92e/41467_2022_28138_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/b5dd3e19b47f/41467_2022_28138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/5a2117af744e/41467_2022_28138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/f29633aea334/41467_2022_28138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/d27065c3dcbc/41467_2022_28138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/9aec71cfa6ee/41467_2022_28138_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/664217e4d280/41467_2022_28138_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/926154d9e93f/41467_2022_28138_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/cb09a79a16a9/41467_2022_28138_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/c2d4d984919a/41467_2022_28138_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f2/8803937/75831edaf92e/41467_2022_28138_Fig10_HTML.jpg

相似文献

1
Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.甲酰肽受体 2 决定非酒精性脂肪性肝病和脂肪性肝炎进展的性别特异性差异。
Nat Commun. 2022 Jan 31;13(1):578. doi: 10.1038/s41467-022-28138-6.
2
Vitronectin deficiency attenuates hepatic fibrosis in a non-alcoholic steatohepatitis-induced mouse model.缺乏血纤连蛋白可减轻非酒精性脂肪性肝炎诱导的小鼠肝纤维化。
Int J Exp Pathol. 2019 Apr;100(2):72-82. doi: 10.1111/iep.12306. Epub 2019 Mar 18.
3
Gender differences in diet-induced steatotic disease in Cyp2b-null mice.Cyp2b 基因缺失小鼠饮食诱导的脂肪性肝病中的性别差异。
PLoS One. 2020 Mar 10;15(3):e0229896. doi: 10.1371/journal.pone.0229896. eCollection 2020.
4
Dysfunction of estrogen-related receptor alpha-dependent hepatic VLDL secretion contributes to sex disparity in NAFLD/NASH development.雌激素相关受体α依赖性肝 VLDL 分泌功能障碍导致 NAFLD/NASH 发展的性别差异。
Theranostics. 2020 Aug 29;10(24):10874-10891. doi: 10.7150/thno.47037. eCollection 2020.
5
Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis.肝小异二聚体伴侣的破坏可诱导实验性非酒精性脂肪性肝炎中脂肪变性和炎症的分离。
J Biol Chem. 2020 Jan 24;295(4):994-1008. doi: 10.1074/jbc.RA119.010233. Epub 2019 Dec 12.
6
Macrophage Raptor Deficiency-Induced Lysosome Dysfunction Exacerbates Nonalcoholic Steatohepatitis.巨噬细胞雷帕霉素靶蛋白缺失诱导溶酶体功能障碍加剧非酒精性脂肪性肝炎。
Cell Mol Gastroenterol Hepatol. 2019;7(1):211-231. doi: 10.1016/j.jcmgh.2018.09.011. Epub 2018 Sep 19.
7
One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver.CDAHFD 诱导的肝脂肪性肝炎和线粒体功能障碍伴氧化应激：一周研究
Int J Mol Sci. 2021 May 29;22(11):5851. doi: 10.3390/ijms22115851.
8
Thrombospondin-I is a critical modulator in non-alcoholic steatohepatitis (NASH).血栓反应蛋白-1 是非酒精性脂肪性肝炎（NASH）的关键调节因子。
PLoS One. 2019 Dec 31;14(12):e0226854. doi: 10.1371/journal.pone.0226854. eCollection 2019.
9
Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat-cholesterol-sugar diet model in mice.在小鼠的高脂肪-高胆固醇-高糖饮食模型中，非酒精性脂肪变性进展为脂肪性肝炎和肝纤维化与促进炎症和肝肿瘤的危险信号的累积平行。
J Transl Med. 2015 Jun 16;13:193. doi: 10.1186/s12967-015-0552-7.
10
Potential Therapeutic Application of Estrogen in Gender Disparity of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.雌激素在非酒精性脂肪性肝病/非酒精性脂肪性肝炎性别差异中的潜在治疗应用。
Cells. 2019 Oct 15;8(10):1259. doi: 10.3390/cells8101259.

引用本文的文献

1
Sex Differences in Risk of Adverse Liver Events in Patients With Cirrhosis.肝硬化患者不良肝脏事件风险的性别差异
JAMA Netw Open. 2025 Jul 1;8(7):e2523674. doi: 10.1001/jamanetworkopen.2025.23674.
2
Resolvin D1-mediated cellular crosstalk protects against MASH.消退素D1介导的细胞间相互作用可预防多器官功能障碍综合征。
JHEP Rep. 2025 May 14;7(8):101454. doi: 10.1016/j.jhepr.2025.101454. eCollection 2025 Aug.
3
High-Fat Diet and Metabolic Diseases: A Comparative Analysis of Sex-Dependent Responses and Mechanisms.高脂饮食与代谢性疾病：性别依赖性反应及机制的比较分析

本文引用的文献

1
Structural basis of ligand binding modes at the human formyl peptide receptor 2.人源甲酰肽受体 2 配体结合模式的结构基础。
Nat Commun. 2020 Mar 5;11(1):1208. doi: 10.1038/s41467-020-15009-1.
2
A bioactive product lipoxin A4 attenuates liver fibrosis in an experimental model by regulating immune response and modulating the expression of regeneration genes.一种生物活性产物脂氧素A4通过调节免疫反应和调控再生基因的表达来减轻实验模型中的肝纤维化。
Turk J Gastroenterol. 2019 Aug;30(8):745-757. doi: 10.5152/tjg.2019.18276.
3
Tumor necrosis factor-inducible gene 6 reprograms hepatic stellate cells into stem-like cells, which ameliorates liver damage in mouse.
Int J Mol Sci. 2025 May 16;26(10):4777. doi: 10.3390/ijms26104777.
4
Association of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with non-alcoholic fatty liver disease and hepatic steatosis in United States adults: insights from NHANES 2017-2020.美国成年人中非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值与非酒精性脂肪性肝病及肝脂肪变性的关联：来自2017 - 2020年美国国家健康与营养检查调查（NHANES）的见解
Front Nutr. 2025 Apr 11;12:1540903. doi: 10.3389/fnut.2025.1540903. eCollection 2025.
5
Exploring the severity and risk factors of non-alcoholic fatty liver disease using the SAF scoring system.使用SAF评分系统探索非酒精性脂肪性肝病的严重程度和危险因素。
Front Med (Lausanne). 2025 Mar 28;12:1510679. doi: 10.3389/fmed.2025.1510679. eCollection 2025.
6
The -formyl peptide receptors: much more than chemoattractant receptors. Relevance in health and disease.甲酰肽受体：远不止是趋化因子受体。在健康与疾病中的意义。
Front Immunol. 2025 Mar 4;16:1568629. doi: 10.3389/fimmu.2025.1568629. eCollection 2025.
7
Formyl peptide receptor 2: a potential therapeutic target for inflammation-related diseases.甲酰肽受体2：炎症相关疾病的潜在治疗靶点。
Pharmacol Rep. 2025 Jun;77(3):593-609. doi: 10.1007/s43440-025-00704-x. Epub 2025 Mar 18.
8
Tetrahydrocurcumin Alleviates Metabolic Dysfunction-Associated Steatohepatitis in Mice by Regulating Serum Lipids, Bile Acids, and Gut Microbiota.四氢姜黄素通过调节血清脂质、胆汁酸和肠道微生物群减轻小鼠代谢功能障碍相关脂肪性肝炎。
Int J Mol Sci. 2025 Jan 22;26(3):895. doi: 10.3390/ijms26030895.
9
BMI trajectories are associated with NAFLD and advanced fibrosis via aging-inflammation mediation.体重指数轨迹通过衰老-炎症介导与非酒精性脂肪性肝病和晚期肝纤维化相关。
BMC Public Health. 2025 Jan 14;25(1):147. doi: 10.1186/s12889-025-21322-5.
10
Estrogen: the forgotten player in metaflammation.雌激素：代谢性炎症中被遗忘的因素。
Front Pharmacol. 2024 Nov 7;15:1478819. doi: 10.3389/fphar.2024.1478819. eCollection 2024.
肿瘤坏死因子诱导基因 6 可将肝星状细胞重编程为干细胞样细胞，从而改善小鼠的肝损伤。
Biomaterials. 2019 Oct;219:119375. doi: 10.1016/j.biomaterials.2019.119375. Epub 2019 Jul 22.
4
Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study.纤维化严重程度是晚期非酒精性脂肪性肝病患者死因特异性死亡率的决定因素：一项多国队列研究。
Gastroenterology. 2018 Aug;155(2):443-457.e17. doi: 10.1053/j.gastro.2018.04.034. Epub 2018 May 5.
5
A simple clinical model predicts incident hepatic steatosis in a community-based cohort: The Framingham Heart Study.一种简单的临床模型可预测基于社区人群的肝脂肪变性事件：弗雷明汉心脏研究。
Liver Int. 2018 Aug;38(8):1495-1503. doi: 10.1111/liv.13709. Epub 2018 Mar 12.
6
Molecular mechanism of estrogen-estrogen receptor signaling.雌激素-雌激素受体信号传导的分子机制。
Reprod Med Biol. 2016 Dec 5;16(1):4-20. doi: 10.1002/rmb2.12006. eCollection 2017 Jan.
7
microRNA-181b is increased in cystic fibrosis cells and impairs lipoxin A receptor-dependent mechanisms of inflammation resolution and antimicrobial defense.miR-181b 在囊性纤维化细胞中增加，并损害脂氧素 A 受体依赖的炎症解决和抗菌防御机制。
Sci Rep. 2017 Oct 18;7(1):13519. doi: 10.1038/s41598-017-14055-y.
8
Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention.非酒精性脂肪性肝病和非酒精性脂肪性肝炎的全球负担：趋势、预测、危险因素和预防。
Nat Rev Gastroenterol Hepatol. 2018 Jan;15(1):11-20. doi: 10.1038/nrgastro.2017.109. Epub 2017 Sep 20.
9
MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1.微小RNA-181b通过靶向沉默信息调节因子1调控非酒精性脂肪性肝病中的脂肪变性。
Biochem Biophys Res Commun. 2017 Nov 4;493(1):227-232. doi: 10.1016/j.bbrc.2017.09.042. Epub 2017 Sep 9.
10
Hepatocellular carcinoma in a mouse model fed a choline-deficient, L-amino acid-defined, high-fat diet.在喂食胆碱缺乏、L-氨基酸限定的高脂肪饮食的小鼠模型中的肝细胞癌。
Int J Exp Pathol. 2017 Aug;98(4):221-233. doi: 10.1111/iep.12240. Epub 2017 Sep 12.