Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, University of Georgia, Athens, GA, 30602, USA.
Department of Pharmacology and Chemical Biology, Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Nat Commun. 2020 Jun 2;11(1):2758. doi: 10.1038/s41467-020-16340-3.
Human beige adipocytes (BAs) have potential utility for the development of therapeutics to treat diabetes and obesity-associated diseases. Although several reports have described the generation of beige adipocytes in vitro, their potential utility in cell therapy and drug discovery has not been reported. Here, we describe the generation of BAs from human adipose-derived stem/stromal cells (ADSCs) in serum-free medium with efficiencies >90%. Molecular profiling of beige adipocytes shows them to be similar to primary BAs isolated from human tissue. In vitro, beige adipocytes exhibit uncoupled mitochondrial respiration and cAMP-induced lipolytic activity. Following transplantation, BAs increase whole-body energy expenditure and oxygen consumption, while reducing body-weight in recipient mice. Finally, we show the therapeutic utility of BAs in a platform for high-throughput drug screening (HTS). These findings demonstrate the potential utility of BAs as a cell therapeutic and as a tool for the identification of drugs to treat metabolic diseases.
人类米色脂肪细胞（BAs）在开发治疗糖尿病和肥胖相关疾病的疗法方面具有潜在的应用价值。尽管已有几篇报道描述了体外生成米色脂肪细胞，但它们在细胞治疗和药物发现方面的潜在应用尚未得到报道。在这里，我们描述了在无血清培养基中从人脂肪来源的干细胞/基质细胞（ADSCs）中高效生成米色脂肪细胞的方法，效率超过 90%。米色脂肪细胞的分子特征分析表明，它们与从人体组织中分离出的原代米色脂肪细胞相似。在体外，米色脂肪细胞表现出解偶联的线粒体呼吸和 cAMP 诱导的脂肪分解活性。移植后，BAs 增加了受体小鼠的全身能量消耗和耗氧量，同时降低了体重。最后，我们展示了 BAs 在高通量药物筛选（HTS）平台中的治疗应用。这些发现表明 BAs 作为细胞治疗剂和鉴定治疗代谢疾病的药物的工具具有潜在的应用价值。
