Metabolic programming of a beige adipocyte phenotype by genistein.
Metabolic programming of a beige adipocyte phenotype by genistein.
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DOI：
10.1002/mnfr.201600574
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发表时间：
2017-02
影响因子：
5.2
通讯作者：
Ford D
中科院分区：
文献类型：
--
作者：
Aziz SA;Wakeling LA;Miwa S;Alberdi G;Hesketh JE;Ford D
促进棕色或米色脂肪组织的发育可以防止肥胖和相关的代谢特征，并且可能是染料木黄酮在小鼠中的保护作用的基础。我们观察到，将染料木黄酮应用于3 T3-L1脂肪细胞将脂质分布从大液滴改变为多室分布，减少了指示白色脂肪细胞的mRNA（ACC、Fasn、Fabp 4、HSL、chemerin和Cumn），并增加了棕色/米色脂肪细胞的特征性mRNA（CD-137和UCP 1）。在脂肪细胞分化中起作用的转录物（Cebpβ、Pgc 1 α、Sirt 1）在应用染料木黄酮后的不同时间达到峰值。这些反应不受雌激素受体（ER）拮抗剂氟维司群的影响，表明染料木素的这种作用不是通过经典的ER途径。Sirt 1抑制剂Ex-527抑制了染料木素介导的UCP 1和Cebpβ mRNA的增加，揭示了Sirt 1在介导该效应中的作用。基线耗氧量和质子泄漏的最大呼吸能力的比例的贡献是更大的细胞暴露于染料木素，表现出更大的线粒体解偶联。我们的结论是，染料木黄酮直接作用于脂肪细胞或脂肪祖细胞的细胞代谢程序，采用米色脂肪细胞的功能。因此，这种天然的膳食剂可以防止肥胖和相关的代谢疾病。
Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. We observed that application of genistein to 3T3‐L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD‐137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpβ, Pgc1α, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex‐527 curtailed the genistein‐mediated increase in UCP1 and Cebpβ mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease.