Key result
Ex vivo browning of white adipose tissue yields brown fat grafts lasting ~8 weeks in mice.
Why the study?
Current approaches to increase brown adipose tissue mass rely on pharmacological compounds that cause undesirable side effects, necessitating alternative methods.
A novel ex vivo tissue-grafting approach successfully converts white adipose tissue to brown adipose tissue, offering a potential non-pharmacological strategy for obesity and diabetes.
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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Blumenfeld et al. (2018) studied Obesity and metabolic disease. exBAT (ex vivo browning of white adipose tissue) vs. White adipose tissue cultured in control media was evaluated on UCP1 expression and maintenance of brown adipose tissue phenotype post-implantation. A single-step ex vivo culture of white adipose tissue fragments with browning factors successfully converted them into brown adipose tissue-like grafts that maintained their phenotype for at least 8 weeks after implantation in mice.
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