title: Dissecting the origin of inducible brown fat in adult humans through a novel adipose stem cell model from adipose tissue surrounding pheochromocytoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a 1-year study to enroll adrenal tumor patients undergoing surgery.
  
  
  METHODS
  The study was conducted at a university hospital.
  
  
  METHODS
  Eight patients operated for pheochromocytoma and three for adrenocortical adenoma participated in the study.
  
  
  METHODS
  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: 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.
authors: Alessandra
authors: A
authors: Di Franco
authors: Daniele
authors: D
authors: Guasti
authors: Benedetta
authors: B
authors: Mazzanti
authors: Tonino
authors: T
authors: Ercolino
authors: Michela
authors: M
authors: Francalanci
authors: Gabriella
authors: G
authors: Nesi
authors: Daniele
authors: D
authors: Bani
authors: Gianni
authors: G
authors: Forti
authors: Massimo
authors: M
authors: Mannelli
authors: Andrea
authors: A
authors: Valeri
authors: Michaela
authors: M
authors: Luconi
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology* / Q000378:metabolism; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology*; D018246:Adrenocortical Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology*; D000071256:Uncoupling Protein 1
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D003470:Culture Media; D007473:Ion Channels; C497417:MYF5 protein, human; D024101:Mitochondrial Proteins; D051787:Myogenic Regulatory Factor 5; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1