Alessandra Di Franco1, Daniele Guasti, Benedetta Mazzanti, Tonino Ercolino, Michela Francalanci, Gabriella Nesi, Daniele Bani, Gianni Forti, Massimo Mannelli, Andrea Valeri, Michaela Luconi. 1. Endocrinology Unit (A.D.F., M.F., G.F., M.M., M.L.), Department of Experimental and Clinical Biomedical Sciences, Histology and Embryology Unit (D.G., D.B.), Department of Experimental and Clinical Medicine, Haematology Unit (B.M.), Department of Experimental and Clinical Medicine, and Division of Pathological Anatomy (G.N.), Department of Surgery and Translational Medicine, University of Florence, and Istituto Toscano Tumori (M.M., M.L.), I-50139 Florence, Italy; Endocrinology Unit (T.E.) and Chirurgia Generale (A.V.), d'Urgenza e Mini-Invasiva, Careggi Hospital, Azienda Ospedaliera Universitaria Careggi, I-50134 Florence, Italy.
Abstract
CONTEXT: The recent discovery of inducible brown adipose tissue (BAT) in adult humans, in which it is involved in controlling adiposity, is pivotal in the development of treatment strategies for obesity. However, the origin of these adipocytes in white adipose tissue (WAT) is still unclear, and no human brown adipose cell models are currently available. OBJECTIVE: The objective of the study was to define the origin of inducible BAT (iBAT) by isolating brown adipose stem cells (B-ASCs) from periadrenal fat in adult patients with catecholamine-secreting pheochromocytoma. DESIGN: This was a 1-year study to enroll adrenal tumor patients undergoing surgery. SETTING: The study was conducted at a university hospital. PATIENTS AND INTERVENTION: Eight patients operated for pheochromocytoma and three for adrenocortical adenoma participated in the study. MAIN OUTCOME MEASURES: Isolation of inducible B-ASCs from fat surrounding the pheochromocytoma was measured. RESULTS: We demonstrated the presence of iBAT islets dispersed in periadrenal WAT in patients operated for pheochromocytoma. From this fat depot, which expresses brite/classical BAT markers and high levels of uncoupling protein-1, we isolated B-ASCs and compared their properties with precursors from sc WAT (S-ASC) of the same patients. B-ASCs showed mesenchymal, stem, and multipotency features and expression of brite/classical BAT markers. When differentiated toward white phenotype, B-ASCs accumulated lipid droplets smaller than S-ASCs and expressed adiponectin. Upon induction of brown differentiation, brown commitment was found only in B-ASCs and not in S-ASCs, with no mature brown adipocytes. CONCLUSIONS: Our findings demonstrate that iBAT developed in periadrenal WAT derives from adult stem cells, unlike WAT precursors, confirming an independent origin of the two fat depots. These stem cells represent a unique in vitro stem cell model to study brown adipogenesis and develop novel antiobesity therapies targeting WAT-BAT conversion.
CONTEXT: The recent discovery of inducible brown adipose tissue (BAT) in adult humans, in which it is involved in controlling adiposity, is pivotal in the development of treatment strategies for obesity. However, the origin of these adipocytes in white adipose tissue (WAT) is still unclear, and no human brown adipose cell models are currently available. OBJECTIVE: The objective of the study was to define the origin of inducible BAT (iBAT) by isolating brown adipose stem cells (B-ASCs) from periadrenal fat in adult patients with catecholamine-secreting pheochromocytoma. DESIGN: This was a 1-year study to enroll adrenal tumorpatients undergoing surgery. SETTING: The study was conducted at a university hospital. PATIENTS AND INTERVENTION: Eight patients operated for pheochromocytoma and three for adrenocortical adenoma participated in the study. MAIN OUTCOME MEASURES: Isolation of inducible B-ASCs from fat surrounding the pheochromocytoma was measured. RESULTS: We demonstrated the presence of iBAT islets dispersed in periadrenal WAT in patients operated for pheochromocytoma. From this fat depot, which expresses brite/classical BAT markers and high levels of uncoupling protein-1, we isolated B-ASCs and compared their properties with precursors from sc WAT (S-ASC) of the same patients. B-ASCs showed mesenchymal, stem, and multipotency features and expression of brite/classical BAT markers. When differentiated toward white phenotype, B-ASCs accumulated lipid droplets smaller than S-ASCs and expressed adiponectin. Upon induction of brown differentiation, brown commitment was found only in B-ASCs and not in S-ASCs, with no mature brown adipocytes. CONCLUSIONS: Our findings demonstrate that iBAT developed in periadrenal WAT derives from adult stem cells, unlike WAT precursors, confirming an independent origin of the two fat depots. These stem cells represent a unique in vitro stem cell model to study brown adipogenesis and develop novel antiobesity therapies targeting WAT-BAT conversion.
Authors: Laurent Vergnes; Graeme R Davies; Jason Y Lin; Michael W Yeh; Masha J Livhits; Avital Harari; Michael E Symonds; Harold S Sacks; Karen Reue Journal: J Clin Endocrinol Metab Date: 2016-08-30 Impact factor: 5.958
Authors: Giulia Cantini; Alessandra Di Franco; Massimo Mannelli; Anthony Scimè; Mario Maggi; Michaela Luconi Journal: Front Cell Dev Biol Date: 2020-05-15