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A direct tissue-grafting approach to increasing endogenous brown fat

Blumenfeld, Nicole R.; Kang, Hwan June; Fenzl, Anna; Song, Ziwei; Chung, Janice Juho; Singh, Ranjodh; Johnson, Roshawn; Karakecili, Ayse; Feranil, Jun B.; Rossen, Ninna S.; Zhang, Vivian; Jaggi, Sahir; McCarty, Bret; Bessler, Steven; Schwartz, Gary J.; Grant, Robert T.; Korner, Judith; Kiefer, Florian W.; Gillette, Brian M.; Sia, Samuel K.

There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled “exBAT”, we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off-target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue-grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism.

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Also Published In

Title
Scientific Reports
DOI
https://doi.org/10.1038/s41598-018-25866-y

More About This Work

Academic Units
Biomedical Engineering
Medicine
Preventative Medicine
Surgery
Published Here
January 31, 2019