下载PDF
{"title":"Extracellular Matrix (ECM) and Fibrosis in Adipose Tissue: Overview and Perspectives.","authors":"Kai Sun, Xin Li, Philipp E Scherer","doi":"10.1002/cphy.c220020","DOIUrl":null,"url":null,"abstract":"<p><p>Fibrosis in adipose tissue is a major driver of obesity-related metabolic dysregulation. It is characterized by an overaccumulation of extracellular matrix (ECM) during unhealthy expansion of adipose tissue in response to over nutrition. In obese adipose-depots, hypoxia stimulates multiple pro-fibrotic signaling pathways in different cell populations, thereby inducing the overproduction of the ECM components, including collagens, noncollagenous proteins, and additional enzymatic components of ECM synthesis. As a consequence, local fibrosis develops. The result of fibrosis-induced mechanical stress not only triggers cell necrosis and inflammation locally in adipose tissue but also leads to system-wide lipotoxicity and insulin resistance. A better understanding of the mechanisms underlying the obesity-induced fibrosis will help design therapeutic approaches to reduce or reverse the pathological changes associated with obese adipose tissue. Here, we aim to summarize the major advances in the field, which include newly identified fibrotic factors, cell populations that contribute to the fibrosis in adipose tissue, as well as novel mechanisms underlying the development of fibrosis. We further discuss the potential therapeutic strategies to target fibrosis in adipose tissue for the treatment of obesity-linked metabolic diseases and cancer. © 2023 American Physiological Society. Compr Physiol 13:4387-4407, 2023.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"13 1","pages":"4387-4407"},"PeriodicalIF":4.2000,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957663/pdf/nihms-1872239.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comprehensive Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cphy.c220020","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
引用
批量引用
Abstract
Fibrosis in adipose tissue is a major driver of obesity-related metabolic dysregulation. It is characterized by an overaccumulation of extracellular matrix (ECM) during unhealthy expansion of adipose tissue in response to over nutrition. In obese adipose-depots, hypoxia stimulates multiple pro-fibrotic signaling pathways in different cell populations, thereby inducing the overproduction of the ECM components, including collagens, noncollagenous proteins, and additional enzymatic components of ECM synthesis. As a consequence, local fibrosis develops. The result of fibrosis-induced mechanical stress not only triggers cell necrosis and inflammation locally in adipose tissue but also leads to system-wide lipotoxicity and insulin resistance. A better understanding of the mechanisms underlying the obesity-induced fibrosis will help design therapeutic approaches to reduce or reverse the pathological changes associated with obese adipose tissue. Here, we aim to summarize the major advances in the field, which include newly identified fibrotic factors, cell populations that contribute to the fibrosis in adipose tissue, as well as novel mechanisms underlying the development of fibrosis. We further discuss the potential therapeutic strategies to target fibrosis in adipose tissue for the treatment of obesity-linked metabolic diseases and cancer. © 2023 American Physiological Society. Compr Physiol 13:4387-4407, 2023.
细胞外基质 (ECM) 和脂肪组织中的纤维化:概述与展望。
脂肪组织纤维化是肥胖相关代谢失调的主要驱动因素。脂肪组织纤维化的特点是细胞外基质(ECM)在脂肪组织因营养过剩而不健康扩张的过程中过度积累。在肥胖的脂肪组织中,缺氧会刺激不同细胞群中的多种促纤维化信号通路,从而诱导 ECM 成分的过度产生,包括胶原蛋白、非胶原蛋白和合成 ECM 的其他酶成分。结果导致局部纤维化。纤维化引起的机械应力不仅会引发脂肪组织局部的细胞坏死和炎症,还会导致整个系统的脂肪毒性和胰岛素抵抗。更好地了解肥胖诱导纤维化的机制将有助于设计治疗方法,减少或逆转与肥胖脂肪组织相关的病理变化。在此,我们旨在总结该领域的主要进展,包括新发现的纤维化因子、导致脂肪组织纤维化的细胞群以及纤维化发展的新机制。我们进一步讨论了针对脂肪组织纤维化的潜在治疗策略,以治疗与肥胖相关的代谢性疾病和癌症。© 2023 美国生理学会。Compr Physiol 13:4387-4407, 2023.
本文章由计算机程序翻译,如有差异,请以英文原文为准。