The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells.
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.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Khanh-Van
KV
Tran
Olga
O
Gealekman
Andrea
A
Frontini
Maria Cristina
MC
Zingaretti
Manrico
M
Morroni
Antonio
A
Giordano
Arianna
A
Smorlesi
Jessica
J
Perugini
Rita
R
De Matteis
Andrea
A
Sbarbati
Silvia
S
Corvera
Saverio
S
Cinti
D052437:Adipocytes, Brown / Q000166:cytology*; D052438:Adipocytes, White / Q000166:cytology*; D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D005697:Galactosides; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008954:Models, Biological; D020286:Pericytes / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D004268:DNA-Binding Proteins; D005697:Galactosides; D007211:Indoles; D014157:Transcription Factors; D000099152:Cadherin 5; C484557:Ebfaz protein, mouse; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside