TMAO promotes disorders of lipid metabolism in psoriasis.

Q3 Medicine

中南大学学报(医学版) Pub Date : 2025-03-28 DOI:10.11817/j.issn.1672-7347.2024.240663

Rao Li, Boyan Hu, Manyun Mao, Wangqing Chen, Wu Zhu

{"title":"TMAO promotes disorders of lipid metabolism in psoriasis.","authors":"Rao Li, Boyan Hu, Manyun Mao, Wangqing Chen, Wu Zhu","doi":"10.11817/j.issn.1672-7347.2024.240663","DOIUrl":null,"url":null,"abstract":"Objectives: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis.Methods: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder.Conclusions: TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"331-343"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"中南大学学报(医学版)","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.11817/j.issn.1672-7347.2024.240663","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis.

Methods: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.

Results: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder.

Conclusions: TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.

查看原文本刊更多论文

氧化三甲胺促进牛皮癣脂质代谢紊乱。

目的：牛皮癣与脂质代谢紊乱有关，但其潜在机制尚不清楚。本研究旨在探讨三甲胺n -氧化物（TMAO）在牛皮癣脂质代谢失调中的作用。方法：采用咪喹莫特（IMQ）诱导的牛皮癣样小鼠模型，评价脂质代谢参数、TMAO水平和肝脏黄素单加氧酶3 (FMO3) mRNA表达。收集健康个体和银屑病患者的血液样本，测量血清TMAO水平和脂质谱。为了阐明TMAO在牛皮癣模型小鼠脂质代谢紊乱中的作用，研究人员通过腹腔注射或饮食给药imq治疗的小鼠外源性TMAO、胆碱或3,3-二甲基-1-丁醇（DMB）。对小鼠模型的肝组织进行RNA测序，以确定tmao调节的信号通路。结果：imq诱导的银屑病小鼠表现出异常的葡萄糖、胰岛素和脂质水平。IMQ处理还下调了葡萄糖转运蛋白2 （Glut2）和沉默信息调节因子1 （Sirt1）的mRNA表达，同时上调了葡萄糖转运蛋白4 （Glut4）和过氧化物酶体增殖物激活受体γ (PPARγ)的mRNA表达。银屑病患者和imq治疗小鼠均观察到血清TMAO水平升高。银屑病小鼠肝脏FMO3 mRNA表达升高。在患者中，TMAO水平与银屑病面积和严重程度指数（PASI）评分、血清甘油三酯（TG）和总胆固醇（TC）水平呈正相关。腹腔注射TMAO加重了imq处理小鼠的脂质失调。富含胆碱的饮食进一步加重了银屑病小鼠的脂质异常和肝损伤，而DMB治疗减轻了这些影响。RNA-Seq分析表明，TMAO上调肝脏microRNA-122 (miR-122)，可能抑制GREM2的表达，从而导致脂质代谢紊乱。结论：TMAO可能通过调节肝脏miR-122/GREM2通路促进银屑病脂质代谢失调。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

中南大学学报(医学版) Medicine-Medicine (all)

CiteScore

1.00

自引率

0.00%

发文量

8237

期刊介绍： Journal of Central South University (Medical Sciences), founded in 1958, is a comprehensive academic journal of medicine and health sponsored by the Ministry of Education and Central South University. The journal has been included in many important databases and authoritative abstract journals at home and abroad, such as the American Medline, Pubmed and its Index Medicus (IM), the Netherlands Medical Abstracts (EM), the American Chemical Abstracts (CA), the WHO Western Pacific Region Medical Index (WPRIM), and the Chinese Science Citation Database (Core Database) (CSCD); it is a statistical source journal of Chinese scientific and technological papers, a Chinese core journal, and a "double-effect" journal of the Chinese Journal Matrix; it is the "2nd, 3rd, and 4th China University Excellent Science and Technology Journal", "2008 China Excellent Science and Technology Journal", "RCCSE China Authoritative Academic Journal (A+)" and Hunan Province's "Top Ten Science and Technology Journals". The purpose of the journal is to reflect the new achievements, new technologies, and new experiences in medical research, medical treatment, and teaching, report new medical trends at home and abroad, promote academic exchanges, improve academic standards, and promote scientific and technological progress.