Human beige adipocytes for drug discovery and cell therapy in metabolic diseases

Amar M. Singh, Liang Zhang, John Avery, Amelia Yin, Yuhong Du, Hui Wang, Zibo Li, Haian Fu, Hang Yin and Stephen Dalton ()
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Amar M. Singh: University of Georgia
Liang Zhang: University of Georgia
John Avery: University of Georgia
Amelia Yin: University of Georgia
Yuhong Du: Emory University School of Medicine
Hui Wang: University of North Carolina Chapel Hill
Zibo Li: University of North Carolina Chapel Hill
Haian Fu: Emory University School of Medicine
Hang Yin: University of Georgia
Stephen Dalton: University of Georgia

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16340-3

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