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A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.pdf (3.76 MB)

A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.

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posted on 2018-04-26, 08:53 authored by C. Fischer, T. Seki, S. Lim, M. Nakamura, P. Andersson, Y. Yang, J. Honek, Y. Wang, Y. Gao, F. Chen, Nilesh J. Samani, J. Zhang, M. Miyake, S. Oyadomari, A. Yasue, X. Li, Y. Zhang, Y. Liu, Y. Cao
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.

History

Citation

Nature Communications, 2017, 8 (2079)

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Nature Communications

Publisher

Nature Publishing Group

eissn

2041-1723

Acceptance date

2017-11-10

Copyright date

2017

Available date

2018-04-26

Publisher version

https://www.nature.com/articles/s41467-017-02158-z.pdf

Language

en

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