Format

Send to

Choose Destination
Nat Commun. 2017 Dec 12;8(1):2079. doi: 10.1038/s41467-017-02158-z.

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

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77, Stockholm, Sweden.
2
Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
3
Hospital of Zhejiang Chinese Medicine University, 54 Youdian Road, Hangzhou, Zhejiang, 310006, China.
4
Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
5
Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
6
Department of Orthodontics Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
7
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.
8
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, 250012, China.
9
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77, Stockholm, Sweden. yihai.cao@ki.se.
10
Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China. yihai.cao@ki.se.
11
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong, 250012, China. yihai.cao@ki.se.

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.

PMID:
29233981
PMCID:
PMC5727036
DOI:
10.1038/s41467-017-02158-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center