ID | 112463 |
著者 |
Fischer, Carina
Karolinska Institute
Seki, Takahiro
Karolinska Institute
Lim, Sharon
Karolinska Institute
Nakamura, Masaki
Karolinska Institute
Andersson, Patrik
Karolinska Institute
Yang, Yunlong
Karolinska Institute
Honek, Jennifer
Karolinska Institute
Wang, Yangang
Qingdao University
Gao, Yanyan
Qingdao University
Chen, Fang
Zhejiang Chinese Medicine University
Samani, Nilesh J.
University of Leicester|Glenfield Hospital
Zhang, Jun
Tokushima University
Li, Xuri
Sun Yat-Sen University
Zhang, Yun
Shandong University
Liu, Yizhi
Sun Yat-Sen University
Cao, Yihai
Karolinska Institute|Qingdao University|Shandong University
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資料タイプ |
学術雑誌論文
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抄録 | Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation. Pharmacological and physiological β-adrenergic stimulation upregulates FGF10 levels and promotes preadipocyte differentiation into beige adipocytes. In vivo local delivery of miR-327 to WATs significantly compromises the beige phenotype and thermogenesis. Contrarily, systemic inhibition of miR-327 in mice induces browning and increases whole-body metabolic rate under thermoneutral conditions. Our data provide mechanistic insight into an autocrine regulatory signaling loop that regulates beige adipocyte formation and suggests that the miR-327–FGF10–FGFR2 signaling axis may be a therapeutic targets for treatment of obesity and metabolic diseases.
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掲載誌名 |
Nature Communications
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ISSN | 20411723
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cat書誌ID | AA12645905
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出版者 | Springer Nature
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巻 | 8
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開始ページ | 2079
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発行日 | 2017-12-12
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備考 | Supplementary Information : ncomms_8_2079_s1.pdf
Peer Review File : ncomms_8_2079_s2.pdf |
権利情報 | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
出版社版
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部局 |
先端酵素学研究所
病院
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