The Vascular Endothelium of the Adipose Tissue Gives Rise to Both White and Brown Fat Cells

• Published in: Cell metabolism 2012-02, Vol.15 (2), p.222-229
• Main Authors: Tran, Khanh-Van, Gealekman, Olga, Frontini, Andrea, Zingaretti, Maria Cristina, Morroni, Manrico, Giordano, Antonio, Smorlesi, Arianna, Perugini, Jessica, De Matteis, Rita, Sbarbati, Andrea, Corvera, Silvia, Cinti, Saverio
• Format: Article
• Language: English
• Subjects: Adipocytes, Brown - cytology; Adipocytes, White - cytology; Adipose Tissue - blood supply; Adipose Tissue - cytology; Animals; Antigens, CD - metabolism; Cadherins - metabolism; Cell Lineage - physiology; DNA-Binding Proteins - metabolism; Endothelial Cells - cytology; Flow Cytometry; Galactosides; Humans; Immunohistochemistry; Indoles; Male; Mice; Microscopy, Electron; Models, Biological; Pericytes - ultrastructure; Rats; Rats, Sprague-Dawley; Stem Cells - cytology; Transcription Factors - metabolism
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2012.01.008

Adipose tissue expansion involves the enlargement of existing adipocytes, the formation of new cells from committed preadipocytes, and the coordinated development of the tissue vascular network. Here we find that murine endothelial cells (ECs) of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-cadherin promoter reveal localization of reporter genes in ECs and also in preadipocytes and adipocytes of white and brown fat depots. Furthermore, capillary sprouts from human adipose tissue, which have predominantly EC characteristics, are found to express Zfp423, a recently identified marker of preadipocyte determination. In response to PPARγ activation, endothelial characteristics of sprouting cells are progressively lost, and cells form structurally and biochemically defined adipocytes. Together these data support an endothelial origin of murine and human adipocytes, suggesting a model for how adipogenesis and angiogenesis are coordinated during adipose tissue expansion. ► Progression of phenotypes from endothelial to preadipose seen in developing adipose tissues ► VE-cadherin promoter-driven tracers are found in adipocytes from white and brown adipose tissues ► Endothelial cells growing from human adipose tissue explants can develop mature adipocyte features ► A population of adipocyte stem cells from white and brown adipose tissue expresses VE-cadherin