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

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.


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Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences
Stephen Dalton Jan 30, 2020 No software was used.
Reads were mapped to the human genome (hg19) by STAR v2.5.3a using default setting and read counts were obtained in STAR quantmode. Gene expression analysis was preformed using limma, Glimma and EdgeR in R Studio The RNA-seq data described in this report has been deposited in the Gene Expression Omnibus under the ID code GSE125331.

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All studies must disclose on these points even when the disclosure is negative. A sample size of n=3 (or more) was used with independent replicates for cell culture experiments. This number of independent replicates is sufficient to determine if the P<0.05, to provide sufficient statistical significance. For statistical significance of mice experiments n=4 (or more), per group was chosen.
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