The recent discovery of the presence of brown adipose tissue (BAT) also in human adults is pivotal for development of anti-obesity therapies. This type of fat, in fact, mainly consists of brite cells (brown adipocytes appearing for a browning process in white fat) which are involved in adiposity control. The origin of brite cells in adult white adipose tissue (WAT) is still unclear as human cell models are lacking.
Our study demonstrated the presence of BAT islets dispersed in periadrenal WAT of adult patients affected by pheochromocytoma tumors, secreting catecholamines. All the enrolled patients affected by pheochromocytoma (n=8, mean±S.D.: 48±19 years for age, 23.8±2.0 kg/m2 for body mass index, BMI), but not the one with adenocortical adenoma, presented extensive BAT islets in the fat surrounding the tumor lesion (uncoupling-protein-1 UCP-1 mean 2ΔΔCt±S.D. of the expression vs GAPDH:150134±106137) and had elevated levels of urinary total metanephrines (normetanephrines+metanephrines mean±S.D.: 4447±1927 μg/24 h) which negatively correlated with BMI (r=0.854, r2=0.730, P=0.007, n=8). From this fat depot, expressing brite and classical markers in addition to high levels of UCP-1, for the first time, we isolated and characterized brown adipose stem cells (B-ASC) and compared their properties with precursors obtained from subcutaneous WAT (S-ASC) of the same patients. B-ASC showed mesenchymal, stem and multipotency features as well as expression of brite/classical markers. When differentiated toward white adipose phenotype, they accumulated more lipid droplets and smaller than the differentiated adipocytes deriving from S-ASC. Using specific brown differentiation cocktails, we could not obtain mature brown adipocytes but brown commitment only in B- and not in S-ASC.
In conclusion, we demonstrated the presence of BAT precursors, different from WAT, in fat surrounding pheochromocytoma lesions, representing a unique in vitro human stem cell model of brown adipose tissue to study brown adipogenesis and browning process.
This study was supported by funds from PRIN2010-11 (prot. 2010C8ERKX, Italian Ministry of University and Research) and from Fondazione Ente Cassa di Risparmio di Pistoia and Pescia.