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- Title
Human beige adipocytes for drug discovery and cell therapy in metabolic diseases.
- Authors
Singh, Amar M.; Zhang, Liang; Avery, John; Yin, Amelia; Du, Yuhong; Wang, Hui; Li, Zibo; Fu, Haian; Yin, Hang; Dalton, Stephen
- Abstract
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. Methods to generate beige adipocytes from a human cell source are inefficient. Here, the authors present a protocol that efficiently generates beige adipocytes from human adipose-derived stem cells (ADSCs), which have potential utility in therapeutic development relating to metabolic diseases such as type 2 diabetes.
- Subjects
ADIPOSE tissue physiology; METABOLIC disorders; FAT cells; CELLULAR therapy; ADIPOGENESIS; HUMAN stem cells; SERUM-free culture media
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-16340-3