Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor.
Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor.
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DOI：
10.1371/journal.pone.0185624
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Hansen JB
中科院分区：
文献类型：
--
作者：
Markussen LK;Isidor MS;Breining P;Andersen ES;Rasmussen NE;Petersen LI;Pedersen SB;Richelsen B;Hansen JB
棕色脂肪组织及其组成的棕色脂肪细胞是代谢紊乱的有前途的治疗靶点，因为它能够耗散能量并改善全身胰岛素敏感性和葡萄糖稳态。棕色脂肪细胞分化和功能的分子控制已在小鼠中进行了广泛的研究，但对人类的这种调节机制知之甚少，部分原因是缺乏人类棕色脂肪组织衍生的细胞模型。在这里，我们使用逆转录病毒介导的过度表达将人端粒酶逆转录酶（TERT）稳定地整合到来自同一供体的深部和浅表人颈部脂肪组织活检的基质血管细胞部分中。棕色和白色前脂肪细胞模型（分别为TERT-hBA和TERT-hWA）至少在第20代之前表现出稳定的增殖率和分化。成熟的TERT-hBA脂肪细胞比成熟的TERT-hWA脂肪细胞表达更高水平的产热标记基因，并表现出更高的最大呼吸能力。 TERT-hBA 脂肪细胞呈 UCP1 阳性，并通过激活 PKA-MKK3/6-p38 MAPK 信号模块并增加产热基因表达和耗氧量来响应 β-肾上腺素能刺激。成熟的 TERT-hWA 脂肪细胞经历了罗格列酮诱导的有效“褐变”，UCP1 和其他富含棕色脂肪细胞的基因的表达强烈增加证明了这一点。总之，TERT-hBA 和 TERT-hWA 细胞模型代表了更好地了解人棕色和白色脂肪细胞分化和功能以及人白色脂肪细胞褐变的分子控制的有用工具。
Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little is known about such regulatory mechanisms in humans, which in part is due to lack of human brown adipose tissue derived cell models. Here, we used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor. The brown and white pre-adipocyte cell models (TERT-hBA and TERT-hWA, respectively) displayed a stable proliferation rate and differentiation until at least passage 20. Mature TERT-hBA adipocytes expressed higher levels of thermogenic marker genes and displayed a higher maximal respiratory capacity than mature TERT-hWA adipocytes. TERT-hBA adipocytes were UCP1-positive and responded to β-adrenergic stimulation by activating the PKA-MKK3/6-p38 MAPK signaling module and increasing thermogenic gene expression and oxygen consumption. Mature TERT-hWA adipocytes underwent efficient rosiglitazone-induced ‘browning’, as demonstrated by strongly increased expression of UCP1 and other brown adipocyte-enriched genes. In summary, the TERT-hBA and TERT-hWA cell models represent useful tools to obtain a better understanding of the molecular control of human brown and white adipocyte differentiation and function as well as of browning of human white adipocytes.
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影响因子：
29
作者：
Ramage LE;Akyol M;Fletcher AM;Forsythe J;Nixon M;Carter RN;van Beek EJ;Morton NM;Walker BR;Stimson RH
通讯作者：
Stimson RH
影响因子：
5.2
作者：
Pisani DF;Djedaini M;Beranger GE;Elabd C;Scheideler M;Ailhaud G;Amri EZ
通讯作者：
Amri EZ
影响因子：
4.8
作者：
Hansen, JB;Petersen, RK;Kristiansen, K
通讯作者：
Kristiansen, K
影响因子：
82.9
作者：
Lidell, Martin E.;Betz, Matthias J.;Enerback, Sven
通讯作者：
Enerback, Sven
影响因子：
3.7
作者：
Murholm M;Dixen K;Qvortrup K;Hansen LH;Amri EZ;Madsen L;Barbatelli G;Quistorff B;Hansen JB
通讯作者：
Hansen JB