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Endocrine Abstracts (2016) 41 GP136 | DOI: 10.1530/endoabs.41.GP136

1University of Florence, Florence, Italy; 2Institute of Applied Physics, Sesto Fiorentino, Italy; 3University of Barcelona, Barcelona, Spain.

The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited brown depots in adult humans, dramatically reduced after birth, solid cell models to study human brown adipogenesis and its pathophysiological regulation are urgently needed.

In our study, we characterized a novel human model of brown adipose stem cells, hfB-ASC, derived from fetal interscapular brown fat depots. After demonstration of the mesenchymal and stem nature of the isolated cells, we studied their differentiation potential, in particular, towards the brown lineage. Following in-vitro induced adipogenesis, these cells exhibit several features of brown fat cells, such as the elevated expression of mature and early brown markers, UCP-1 and PRDM16, respectively (2−ΔΔCt: 2295±864 and 19.3±8.0 for UCP-1 and PRDM16), but not of white markers as leptin, compared to in-vitro differentiated white adipose stem cells. They maintain also a specific intrinsic differentiation program to functional brown adipocytes, and even spontaneously organize in organoid structures with brown features. Moreover, for the first time, we investigated the thermogenic and electrophysiological activity of the in-vitro-derived fetal brown adipocytes compared to their undifferentiated hfB-ASC precursors, in basal conditions and after acute administration of norepinephrine. Compared to adipocytes obtained from in-vitro differentiation of white adipose stem cells, brown adipocytes from hfB-ASC show a significantly increase in temperature vs. undifferentiated cells (Δtemperature: 0.30 °C±0.10, P=0.02), as well as following acute administration of 10 μM norepinephrine (Δtemperature: 0.21 °C±0.20, P=0.02).

In conclusion, starting from interscapular brown fat of human fetus, we developed and functionally characterized a novel physiological brown adipose stem cell model. This model may represent a unique opportunity for further studies on brown adipogenesis processes in humans, as well as the most suitable target to develop novel therapeutic approaches in order to stimulate brown activity in metabolic pathologies.

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