He Yufei, Liang Zhuokai, Wang Jing, Tang Haojing, Li Jian, Cai Junrong, Liao Yunjun
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Front Bioeng Biotechnol. 2022 Aug 15;10:905194. doi: 10.3389/fbioe.2022.905194. eCollection 2022.
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 . 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 , suitable for mechanistic studies of adipose biology and development of cell and drug therapies in the future.
过多且功能失调的脂肪组织在包括肥胖症、动脉粥样硬化和2型糖尿病在内的代谢性疾病中起重要作用。在哺乳动物中,脂肪组织分为两种类型:白色脂肪组织和棕色脂肪组织。成年棕色组织主要由米色脂肪细胞组成,这些细胞将储存的能量以热量形式消耗掉,并且作为肥胖症的治疗靶点越来越受到关注。然而,仍然缺乏能够使成熟白色脂肪细胞转分化为米色脂肪细胞的细胞模型。在此,我们描述了一种基于悬顶培养的新型人类成熟白色脂肪细胞模型,该模型在悬顶培养的机械力和缺氧条件下转分化为米色脂肪细胞。我们还表明,使用罗格列酮和雷帕霉素可以调节转分化,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,这些源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,与脂肪来源的干细胞相比,成熟脂肪细胞特异性基因的表达更高。总体而言,我们报告了一种从白色脂肪细胞方便地培养米色脂肪细胞的新方法,适用于未来脂肪生物学的机制研究以及细胞和药物疗法的开发。