Differentiation of Human Adipose-Derived Stem Cells into "Brite" (Brown-in-White) Adipocytes.
Differentiation of Human Adipose-Derived Stem Cells into "Brite" (Brown-in-White) Adipocytes.
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DOI：
10.3389/fendo.2011.00087
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发表时间：
2011
影响因子：
5.2
通讯作者：
Amri EZ
中科院分区：
文献类型：
--
作者：
Pisani DF;Djedaini M;Beranger GE;Elabd C;Scheideler M;Ailhaud G;Amri EZ
现已证实成年人具有活性棕色脂肪组织（BAT），其代表对抗肥胖和相关疾病的潜在药理学靶标。此外，在β3肾上腺素能刺激下，小鼠白色脂肪组织（WAT）中也出现产热棕色样脂肪细胞（“brite脂肪细胞”）。我们先前已经证明，人多能脂肪源性干细胞（hMADS）能够分化为表现出人白色脂肪细胞的关键特性的细胞，然后在PPARγ活化后转化为功能性棕色脂肪细胞。鉴于大量数据表明来自BAT和WAT的产热脂肪细胞具有不同的细胞来源，我们在分子水平上将来自两种性别的UCP 1阳性hMADS脂肪细胞表征为brite脂肪细胞。白色至棕色hMADS脂肪细胞的转化依赖于以罗格列酮作为最有效激动剂的PPARγ活化，并被PPARγ拮抗剂抑制。与小鼠细胞模型相反，hMADS细胞转化为棕色脂肪细胞是由BMP 7处理弱诱导的，并且不受Hedgehog途径激活的调节。到目前为止，还没有获得人棕色脂肪细胞的原代或克隆前体细胞，可以用作开发治疗药物的工具，并进一步了解人类棕色脂肪形成的分子机制。因此，hMADS细胞代表了一种合适的人类细胞模型，以描述棕色/棕色脂肪细胞的形成和/或解偶联能力，这可能有助于消散个体中的热量过量摄入。
It is well established now that adult humans possess active brown adipose tissue (BAT) which represents a potential pharmacological target to combat obesity and associated diseases. Moreover thermogenic brown-like adipocytes (“brite adipocytes”) appear also in mouse white adipose tissue (WAT) upon β3-adrenergic stimulation. We had previously shown that human multipotent adipose-derived stem cells (hMADS) are able to differentiate into cells which exhibit the key properties of human white adipocytes, and then to convert into functional brown adipocytes upon PPARγ activation. In light of a wealth of data indicating that thermogenic adipocytes from BAT and WAT have a distinct cellular origin, we have characterized at the molecular level UCP1 positive hMADS adipocytes from both sexes as brite adipocytes. Conversion of white to brown hMADS adipocytes is dependent on PPARγ activation with rosiglitazone as the most potent agonist and is inhibited by a PPARγ antagonist. In contrast to mouse cellular models, hMADS cells conversion into brown adipocytes is weakly induced by BMP7 treatment and not modulated by activation of the Hedgehog pathway. So far no primary or clonal precursor cells of human brown adipocytes have been obtained that can be used as a tool to develop therapeutic drugs and to gain further insights into the molecular mechanisms of brown adipogenesis in humans. Thus hMADS cells represent a suitable human cell model to delineate the formation and/or the uncoupling capacity of brown/brite adipocytes that could help to dissipate caloric excess intake among individuals.