A reservoir of brown adipocyte progenitors in human skeletal muscle
A reservoir of brown adipocyte progenitors in human skeletal muscle
复制标题
DOI：
10.1634/stemcells.2008-0325
复制
发表时间：
2008-09-01
期刊：
影响因子：
5.2
通讯作者：
Giacobino, Jean-Paul
中科院分区：
文献类型：
--
作者：
Crisan, Mihaela;Casteilla, Louis;Giacobino, Jean-Paul
棕色脂肪组织解偶联蛋白-1（UCP 1）在啮齿类动物能量平衡的调控中起重要作用。然而，长期以来人们一直认为，在成年人中没有生理相关的UCP 1表达。在这项研究中，我们表明，使用原始的方法，包括从各种组织中分选细胞，并在成脂培养基中分化它们，表达CD 34表面蛋白的骨骼肌细胞的固定群体可以在体外分化成真正的棕色脂肪细胞，具有高水平的UCP 1表达和非偶联呼吸。这些细胞可以在培养中扩增，并且它们的UCP 1 mRNA表达通过细胞渗透性cAMP衍生物和过氧化物酶体增殖物激活受体-γ（PPAR γ）激动剂强烈增加。此外，在成年人的骨骼肌中检测到UCP 1 mRNA，并且其表达通过PPAR γ激动剂治疗在体内增加。迄今为止，所有关于UCP 1在成年人中表达的研究都集中在白色脂肪组织上。在这里，我们第一次展示了在人类骨骼肌中的存在和具有高UCP 1表达潜力的祖细胞的前瞻性分离。这个水库的发现产生了一个新的希望，治疗肥胖的能量耗散。
Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-gamma (PPAR gamma) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR gamma agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.