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
資料タイプ
学術雑誌論文
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.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
8
開始ページ
2079
発行日
2017-12-12
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/.
EDB ID
337838
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
病院