miR-125a-3p在小鼠的成脂分化过程中调节促炎因子FSTL1的表达,抑制脂肪生成

IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY FASEB Journal Pub Date : 2023-08-16 DOI:10.1096/fj.202300851R
Haifeng Liu, Jie Wen, Xue Tian, Tong Li, Ju Zhao, Jingjing Cheng, Lishi Huang, Ye Zhao, Quanquan Cao, Jun Jiang
{"title":"miR-125a-3p在小鼠的成脂分化过程中调节促炎因子FSTL1的表达,抑制脂肪生成","authors":"Haifeng Liu,&nbsp;Jie Wen,&nbsp;Xue Tian,&nbsp;Tong Li,&nbsp;Ju Zhao,&nbsp;Jingjing Cheng,&nbsp;Lishi Huang,&nbsp;Ye Zhao,&nbsp;Quanquan Cao,&nbsp;Jun Jiang","doi":"10.1096/fj.202300851R","DOIUrl":null,"url":null,"abstract":"<p>Adipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low-grade chronic inflammatory disease. Follistatin-like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain- and loss-of-function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro-inflammatory factors IL-1β and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR-125a-3p targeted the 3′ UTR region of FSTL1. These results demonstrated that miR-125a-3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR-125a-3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL-1β and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR-125a-3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte-induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR-125a-3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity-related inflammatory diseases.</p>","PeriodicalId":50455,"journal":{"name":"FASEB Journal","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"miR-125a-3p regulates the expression of FSTL1, a pro-inflammatory factor, during adipogenic differentiation, and inhibits adipogenesis in mice\",\"authors\":\"Haifeng Liu,&nbsp;Jie Wen,&nbsp;Xue Tian,&nbsp;Tong Li,&nbsp;Ju Zhao,&nbsp;Jingjing Cheng,&nbsp;Lishi Huang,&nbsp;Ye Zhao,&nbsp;Quanquan Cao,&nbsp;Jun Jiang\",\"doi\":\"10.1096/fj.202300851R\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Adipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low-grade chronic inflammatory disease. Follistatin-like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain- and loss-of-function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro-inflammatory factors IL-1β and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR-125a-3p targeted the 3′ UTR region of FSTL1. These results demonstrated that miR-125a-3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR-125a-3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL-1β and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR-125a-3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte-induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR-125a-3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity-related inflammatory diseases.</p>\",\"PeriodicalId\":50455,\"journal\":{\"name\":\"FASEB Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2023-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"FASEB Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1096/fj.202300851R\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1096/fj.202300851R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

脂肪的形成受到多种因素的严格调控,包括基因和microrna。肥胖是一种低度慢性炎症性疾病,脂肪沉积过多是肥胖的主要特征。卵泡抑素样1 (Follistatin-like 1, FSTL1)是多种炎症性疾病的重要调节因子。然而,FSTL1在前脂肪细胞分化和炎症反应中的潜在机制尚不清楚。本研究旨在探讨FSTL1在小鼠皮下前脂肪细胞分化中的生物学功能及其潜在机制。我们发现FSTL1在分化早期高表达,随后急剧下降,这表明FSTL1可能在脂肪形成中起作用。同时,功能增益和功能缺失实验表明,FSTL1不仅通过诱导促炎因子IL-1β和CCL2的表达参与炎症反应,而且还能显著减弱前脂肪细胞的分化,这可以通过降低脂质积累和脂肪形成基因(包括PPARγ和FABP4)的水平来证明。此外,靶基因预测和荧光素酶报告基因实验验证了miR-125a-3p靶向FSTL1的3 ' UTR区域。这些结果表明,miR-125a-3p在mRNA和蛋白水平上负调控FSTL1的表达。此外,在脂肪前细胞中过表达miR-125a-3p可显著加速成脂分化,并下调IL-1β和CCL2的水平,这与FSTL1的下调一致。相反,用miR-125a-3p抑制剂治疗可以减轻脂肪形成,但会诱导炎症基因的表达。综上所述,本研究提示FSTL1在脂肪细胞诱导的炎症中具有积极作用,并负向调节前脂肪细胞分化。进一步的研究表明,miR-125a-3p可以通过靶向FSTL1逆转这种作用,这可能为治疗肥胖相关炎症性疾病提供更好的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
miR-125a-3p regulates the expression of FSTL1, a pro-inflammatory factor, during adipogenic differentiation, and inhibits adipogenesis in mice

Adipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low-grade chronic inflammatory disease. Follistatin-like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain- and loss-of-function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro-inflammatory factors IL-1β and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR-125a-3p targeted the 3′ UTR region of FSTL1. These results demonstrated that miR-125a-3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR-125a-3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL-1β and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR-125a-3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte-induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR-125a-3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity-related inflammatory diseases.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
FASEB Journal
FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
期刊最新文献
Exosomal let-7b-5p deriving from parietal epithelial cells attenuate renal fibrosis through suppression of TGFβR1 and ARID3a in obstructive kidney disease. Spatially restricted ecto-5'-nucleotidase expression promotes the growth of uterine leiomyomas by modulating Akt activity. Axon guidance genes are regulated by TDP-43 and RGNEF through long-intron removal. Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis. Effects of unilateral nasal obstruction on mandibular condyle in mice of different ages: An exploration based on H-type angiogenesis coupling osteogenesis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1