Inducible Brown Adipogenesis of Supraclavicular Fat in Adult Humans

Inducible Brown Adipogenesis of Supraclavicular Fat in Adult Humans
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DOI:
10.1210/en.2011-1349
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发表时间:
2011-10-01
期刊:
影响因子:
4.8
通讯作者:
Ho, Ken K. Y.
Ho, Ken K. Y.
中科院分区:
医学2区
文献类型:
--
作者:
Lee, Paul;Swarbrick, Michael M.;Ho, Ken K. Y.

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棕色脂肪组织(BAT)在啮齿类动物产热和能量平衡中起着重要作用。使用正电子发射断层扫描(PET)-计算机断层扫描的代谢成像已经确定了BAT在成年人锁骨上窝中的重要储存库。锁骨上脂肪是否含有前体棕色脂肪细胞尚不清楚。本研究的目的是确定人锁骨上脂肪中前体细胞的成脂潜能。在PET-计算机断层扫描的指导下,我们从六个人的锁骨上窝获得脂肪活检,配对的皮下脂肪活检作为阴性对照。将每块脂肪组织分开并进行组织学、基因分析和原代培养。在培养物中检查细胞的形态学变化,并在完全分化后收获RNA和蛋白质用于分析UCP 1水平。锁骨上脂肪的组织学/分子分析显示PET阳性个体的BAT丰度高于PET阴性个体。在所有受试者中,从锁骨上脂肪分离的成纤维细胞样细胞在体外分化,并均匀地分化为含有多小叶脂滴的脂肪细胞,表达高水平的UCP 1。PET阳性和PET阴性来源的样品从接种到出现成纤维细胞样细胞所需的总时间分别为32-34和40-42 d,而无论PET状态如何,实现完全分化所需的时间为7 d。皮下脂肪的前体细胞不能增殖或表达UCP 1。总之,从锁骨上脂肪分离的前脂肪细胞能够在体外分化成棕色脂肪细胞,而不管PET状态如何。这项研究首次提供了成年人锁骨上区域可诱导棕色脂肪形成的证据。(内分泌学152:3597-3602,2011)
Brown adipose tissue (BAT) plays key roles in thermogenesis and energy homeostasis in rodents. Metabolic imaging using positron emission tomography (PET)-computer tomography has identified significant depots of BAT in the supraclavicular fossa of adult humans. Whether supraclavicular fat contains precursor brown adipocytes is unknown. The aim of the present study was to determine the adipogenic potential of precursor cells in human supraclavicular fat. We obtained fat biopsies from the supraclavicular fossa of six individuals, as guided by PET-computer tomography, with paired sc fat biopsies as negative controls. Each piece of fat tissue was divided and processed for histology, gene analysis, and primary culture. Cells were examined for morphological changes in culture and harvested for RNA and protein upon full differentiation for analysis of UCP1 level. Histological/molecular analysis of supraclavicular fat revealed higher abundance of BAT in PET-positive than PET-negative individuals. In all subjects, fibroblast-like cells isolated from supraclavicular fat differentiated in vitro and uniformly into adipocytes containing multilobulated lipid droplets, expressing high level of UCP1. The total duration required from inoculation to emergence of fibroblast-like cells was 32-34 and 40-42 d for PET-positive-and PET-negative-derived samples, respectively, whereas the time required to achieve full differentiation was 7 d, regardless of PET status. Precursor cells from sc fat failed to proliferate or express UCP1. In summary, preadipocytes isolated from supraclavicular fat are capable of differentiating into brown adipocytes in vitro, regardless of PET status. This study provides the first evidence of inducible brown adipogenesis in the supraclavicular region in adult humans. (Endocrinology 152: 3597-3602, 2011)