Ceiling culture of human mature white adipocytes with a browning agent: A novel approach to induce transdifferentiation into beige adipocytes.

Ceiling culture of human mature white adipocytes with a browning agent: A novel approach to induce transdifferentiation into beige adipocytes.
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使用褐变剂对人类成熟白色脂肪细胞进行天花板培养:诱导转分化为米色脂肪细胞的新方法

DOI:
10.3389/fbioe.2022.905194
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发表时间:
2022
影响因子:
5.7
通讯作者:
Liao, Yunjun
Liao, Yunjun
中科院分区:
工程技术2区
文献类型:
--
作者:
He, Yufei;Liang, Zhuokai;Wang, Jing;Tang, Haojing;Li, Jian;Cai, Junrong;Liao, Yunjun

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过量和功能失调的脂肪组织在代谢性疾病中起重要作用,包括肥胖、动脉粥样硬化和2型糖尿病。在哺乳动物中,脂肪组织分为两种类型:白色和棕色。成人棕色组织主要由米色脂肪细胞组成,其将储存的能量转化为热量,并且作为肥胖症的治疗靶点越来越受欢迎。然而,仍然缺乏允许成熟白色脂肪细胞转分化为米色脂肪细胞的细胞模型,如在体内所见。在这里,我们描述了一种新的,天花板培养为基础的模型,人类成熟的白色脂肪细胞,转分化成米色脂肪细胞的机械力和缺氧的天花板培养。我们还表明,罗格列酮和雷帕霉素的使用可以调节转分化,分别上调和下调米色脂肪细胞特异性基因的表达。罗格列酮还促进了脂肪酸脂解和氧化基因的上调。最后,这些来自去分化脂肪细胞的米色脂肪细胞表现出祖细胞特异性表型,成熟脂肪细胞特异性基因的表达高于脂肪细胞来源的干细胞。总之,我们报告了一种新的方法,方便地培养米色脂肪细胞从白色脂肪细胞在体外,适合脂肪生物学的机制研究和细胞和药物治疗的发展在未来。
Excess and dysfunctional adipose tissue plays an important role in metabolic diseases, including obesity, atherosclerosis and type 2 diabetes mellitus. In mammals, adipose tissue is categorized into two types: white and brown. Adult brown tissue is mainly composed of beige adipocytes, which dispose of stored energy as heat and have become increasingly popular as a therapeutic target for obesity. However, there is still a paucity of cell models that allow transdifferentiation of mature white adipocytes into beige adipocytes, as seen in vivo. Here, we describe a novel, ceiling culture-based model of human mature white adipocytes, which transdifferentiate into beige adipocytes under the mechanical force and hypoxia of ceiling culture. We also show that the use of rosiglitazone and rapamycin can modulate transdifferentiation, up and down regulating expression of beige adipocyte-specific genes, respectively. Rosiglitazone additionally facilitated the upregulation of fatty acid lipolysis and oxidation genes. Finally, these beige adipocytes derived from dedifferentiated adipocytes exhibited a progenitor-specific phenotype, with higher expression of mature adipocyte-specific genes than adipocyte-derived stem cells. Overall, we report a novel approach to conveniently cultivate beige adipocytes from white adipocytes in vitro, suitable for mechanistic studies of adipose biology and development of cell and drug therapies in the future.
棕色和米色脂肪组织:肥胖和 2 型糖尿病的新型治疗策略
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