期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02158-z
关键词
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资金
- Swedish Research Council
- Swedish Cancer Foundation
- Karolinska Institute Foundation
- Torsten Soderberg Foundation
- European Research Council (ERC) advanced grant ANGIOFAT [250021]
- NOVO Nordisk Foundation
- Royal Alice Wallenberg Foundation
- KID
- Grants-in-Aid for Scientific Research [16H05222, 17K09862, 16K15237, 16H05551] Funding Source: KAKEN
- Novo Nordisk Fonden [NNF14OC0012835] Funding Source: researchfish
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 beta-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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