A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.
A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.
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DOI：
10.1038/s41467-017-02158-z
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发表时间：
2017-12-12
影响因子：
16.6
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Fischer C;Seki T;Lim S;Nakamura M;Andersson P;Yang Y;Honek J;Wang Y;Gao Y;Chen F;Samani NJ;Zhang J;Miyake M;Oyadomari S;Yasue A;Li X;Zhang Y;Liu Y;Cao Y
了解调节米色脂肪细胞形成的分子机制可能会导致对抗肥胖的新疗法的发展。在这里，我们报告了一个基于miRNA的自分泌调节途径，控制前脂肪细胞分化为米色脂肪细胞。我们确定miR-327是在促进小鼠白色脂肪组织（WAT）布朗宁的条件下基质-血管部分（SVF）中靶向生长因子的下调最多的miRNA之一。功能获得和功能丧失实验表明，miR-327靶向FGF 10以防止米色脂肪细胞分化。药理学和生理学β-肾上腺素能刺激上调FGF 10水平并促进前脂肪细胞分化为米色脂肪细胞。体内局部递送miR-327至WAT显著损害米色表型和产热。因此，在热中性条件下，小鼠中miR-327的全身抑制诱导布朗宁并增加全身代谢率。我们的数据提供了对调节米色脂肪细胞形成的自分泌调节信号环的机制见解，并表明miR-327-FGF 10-FGFR 2信号轴可能是治疗肥胖和代谢疾病的治疗靶点。白色脂肪细胞可以在一个被称为beiging的过程中被刺激表达产热基因。在这里，作者表明，miR-327在beiging过程中下调，这释放了FGF 10的抑制作用，并通过FGFR 2的信号传导支持米色脂肪细胞的形成。
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. White adipocytes can be stimulated to express thermogenic genes in a process known as beiging. Here, the authors show that miR-327 is downregulated during beiging, which releases FGF10 from inhibition and supports beige adipocyte formation via signaling through FGFR2.
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影响因子：
120.1
作者：
Cao, Yihai
通讯作者：
Cao, Yihai
影响因子：
5.2
作者：
Itoh N;Ohta H;Konishi M
通讯作者：
Konishi M
影响因子：
3.3
作者：
Cohen P;Spiegelman BM
通讯作者：
Spiegelman BM
影响因子：
64.5
作者：
Cohen P;Levy JD;Zhang Y;Frontini A;Kolodin DP;Svensson KJ;Lo JC;Zeng X;Ye L;Khandekar MJ;Wu J;Gunawardana SC;Banks AS;Camporez JP;Jurczak MJ;Kajimura S;Piston DW;Mathis D;Cinti S;Shulman GI;Seale P;Spiegelman BM
通讯作者：
Spiegelman BM
影响因子：
82.9
作者：
Lidell, Martin E.;Betz, Matthias J.;Enerback, Sven
通讯作者：
Enerback, Sven