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A miR-327-FGF10-FGF...
A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning
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- Fischer, C (author)
- Karolinska Institutet
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- Seki, T (author)
- Karolinska Institutet
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Lim, S (author)
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Nakamura, M (author)
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- Andersson, P (author)
- Karolinska Institutet
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Yang, YL (author)
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Honek, J (author)
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Wang, YG (author)
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Gao, YY (author)
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Chen, F (author)
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Samani, NJ (author)
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Zhang, J (author)
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Miyake, M (author)
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Oyadomari, S (author)
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Yasue, A (author)
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Li, XR (author)
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Zhang, Y (author)
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Liu, YZ (author)
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- Cao, YH (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-12-12
- 2017
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 2079-
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Abstract
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- 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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- art (subject category)
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To the university's database
- By the author/editor
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Fischer, C
-
Seki, T
-
Lim, S
-
Nakamura, M
-
Andersson, P
-
Yang, YL
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show more...
-
Honek, J
-
Wang, YG
-
Gao, YY
-
Chen, F
-
Samani, NJ
-
Zhang, J
-
Miyake, M
-
Oyadomari, S
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Yasue, A
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Li, XR
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Zhang, Y
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Liu, YZ
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Cao, YH
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show less...
- Articles in the publication
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Nature communica ...
- By the university
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Karolinska Institutet