Thyroid Stimulating Hormone May Facilitates Adipose Tissue Insulin Resistance by Inducing M1 Macrophage Polarization.

IF 4.2 2区医学 Q2 IMMUNOLOGY

Journal of Inflammation Research Pub Date : 2025-06-25 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S522062

Mengfei Fu, Hanyu Wang, Yuhan Zhang, Liu Yang, Yang Chen, Xiao Chen, Zixuan Wang, Hui Sun

{"title":"Thyroid Stimulating Hormone May Facilitates Adipose Tissue Insulin Resistance by Inducing M1 Macrophage Polarization.","authors":"Mengfei Fu, Hanyu Wang, Yuhan Zhang, Liu Yang, Yang Chen, Xiao Chen, Zixuan Wang, Hui Sun","doi":"10.2147/JIR.S522062","DOIUrl":null,"url":null,"abstract":"Background: Recent studies suggest connection between the thyroid stimulating hormone (TSH) and insulin resistance (IR). Adipose tissue is one of insulin's target tissues. However, currently the regulatory mechanism of TSH on the adipose tissue is not fully investigated yet.Methods: We constructed a subclinical hypothyroidism (SCH) mouse model induced by methimazole with elevated TSH levels and then observed its metabolic profile, adipose tissue IR, and the adipose tissue macrophages (ATMs) phenotype. In vitro, we treated RAW264.7 cells and bone marrow-derived macrophages (BMDM) to assess the effect of TSH on macrophage polarization and explore the specific underlying mechanisms.Results: SCH mice exhibited a poorer metabolic profile and an advanced adipose tissue IR. Meanwhile, the number of M1 ATMs was increased in SCH mice adipose tissue. In vitro, TSH induced endoplasmic reticulum stress in macrophages, which activated the GRP78-ATF6-CHOP signaling pathway, and further promoted M1 macrophage polarization. 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum stress inhibitor, corrected the polarization imbalance of ATMs in SCH mice adipose tissue and improved adipose tissue dysfunction and IR.Conclusion: TSH activated endoplasmic reticulum stress in macrophages, which induced the polarization of ATMs toward a pro-inflammatory M1 phenotype and promotes adipose tissue IR. Our findings highlight the possible relationship of TSH with immunity and metabolism.","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8331-8343"},"PeriodicalIF":4.2000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206420/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S522062","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Recent studies suggest connection between the thyroid stimulating hormone (TSH) and insulin resistance (IR). Adipose tissue is one of insulin's target tissues. However, currently the regulatory mechanism of TSH on the adipose tissue is not fully investigated yet.

Methods: We constructed a subclinical hypothyroidism (SCH) mouse model induced by methimazole with elevated TSH levels and then observed its metabolic profile, adipose tissue IR, and the adipose tissue macrophages (ATMs) phenotype. In vitro, we treated RAW264.7 cells and bone marrow-derived macrophages (BMDM) to assess the effect of TSH on macrophage polarization and explore the specific underlying mechanisms.

Results: SCH mice exhibited a poorer metabolic profile and an advanced adipose tissue IR. Meanwhile, the number of M1 ATMs was increased in SCH mice adipose tissue. In vitro, TSH induced endoplasmic reticulum stress in macrophages, which activated the GRP78-ATF6-CHOP signaling pathway, and further promoted M1 macrophage polarization. 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum stress inhibitor, corrected the polarization imbalance of ATMs in SCH mice adipose tissue and improved adipose tissue dysfunction and IR.

Conclusion: TSH activated endoplasmic reticulum stress in macrophages, which induced the polarization of ATMs toward a pro-inflammatory M1 phenotype and promotes adipose tissue IR. Our findings highlight the possible relationship of TSH with immunity and metabolism.

查看原文本刊更多论文

促甲状腺激素可能通过诱导M1巨噬细胞极化促进脂肪组织胰岛素抵抗。

背景：近年来的研究表明促甲状腺激素（TSH）与胰岛素抵抗（IR）之间存在联系。脂肪组织是胰岛素的靶组织之一。然而，目前对TSH对脂肪组织的调节机制还没有充分的研究。方法：建立甲巯咪唑诱导的亚临床甲状腺功能减退（SCH）小鼠模型，观察其代谢谱、脂肪组织IR和脂肪组织巨噬细胞（ATMs）表型。我们在体外对RAW264.7细胞和骨髓源性巨噬细胞（bone marrow macrophages， BMDM）进行处理，评估TSH对巨噬细胞极化的影响，并探讨其具体机制。结果：SCH小鼠表现出较差的代谢谱和先进的脂肪组织IR。同时，SCH小鼠脂肪组织中M1 ATMs的数量增加。在体外，TSH诱导巨噬细胞内质网应激，激活GRP78-ATF6-CHOP信号通路，进一步促进M1巨噬细胞极化。内质网应激抑制剂4-苯基丁酸（4-PBA）可纠正SCH小鼠脂肪组织ATMs极化失衡，改善脂肪组织功能障碍和IR。结论：TSH激活巨噬细胞内质网应激，诱导ATMs向促炎M1表型极化，促进脂肪组织IR。我们的发现强调了TSH与免疫和代谢的可能关系。

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

Journal of Inflammation Research Immunology and Microbiology-Immunology

CiteScore

6.10

自引率

2.20%

发文量

658

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.