We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.
- Authors
Fischer, Carina; Takahiro Seki; Sharon Lim; Masaki Nakamura; Andersson, Patrik; Yunlong Yang; Honek, Jennifer; Yihai Cao; Yangang Wang; Yanyan Gao; Fang Chen; Samani, Nilesh J.; Jun Zhang; Masato Miyake; Seiichi Oyadomari; Yasue, Akihiro; Xuri Li; Yizhi Liu; Yun Zhang
- Abstract
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.
- Subjects
FAT cells; OBESITY; MICRORNA; WHITE adipose tissue; PHARMACOLOGY
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-02158-z