Metabolism: Fat discovers a new ancestor
Nature Reviews Molecular Cell Biology 13, 207-208, (April 2012)
The expansion of adipose tissue needs to be coordinated with growth of the vasculature, but exactly how this occurs was unclear. Cinti and colleagues shed some light onto this problem and reveal that endothelial cells (ECs) in adipose tissue capillaries can give rise to white and brown adipocytes.
Analysis of the morphology of mouse epididymal white adipose tissue (eWAT) at postnatal days 6–8 (P6–8), when adipocytes have begun to form, led the authors to hypothesize that ECs may give rise to adipocytes. To examine this, they carried out lineage-tracing experiments using mice in which activation of the promoter for the endothelial marker vascular endothelial (VE)-cadherin is detected via X-gal staining. In addition to ECs, at P6–8, adipocytes in eWAT and subcutaneous WAT were positive for X-gal. Interestingly, X-gal staining was also observed in the interscapular brown fat depot, and, consistently, it colocalized with uncoupling protein 1 (UCP1), a brown adipocyte marker.
To exclude the possibility that the adipocyte precursors are cells of haematopoietic origin (some of which also express VE-cadherin), the authors carried out lineage-tracing studies using mice in which cells derived from haematopoietic precursors are not labelled. Once again, X-gal staining was observed in capillaries as well as adipocytes in eWAT, inguinal and brown adipose depots.
Finally, the authors asked whether human adipocytes also originate from ECs or EC-like cells. To this end, they cultured fragments of human adipose tissue, which, as previously shown, gives rise to capillary sprouts when pro-angiogenic medium is added. Following treatment with an agonist of peroxisome proliferator-activated receptor-γ (PPARγ; the master regulator of adipogenesis), cells within the capillary sprouts produced lipid droplets and had white adipocyte features. Moreover, these cells showed decreased expression of mRNAs encoding EC proteins and increased expression of mRNAs encoding adipocyte proteins, including the transcription factor zinc-finger protein 423 (ZFP423), a marker of adipogenic cells.
Together, these findings reveal that white and brown adipocytes can arise from ECs or EC-like cells. Previous work had shown that adipocytes can acquire an EC phenotype in vitro, which indicates that the fate of the two cell types may be plastic to maintain homeostasis during adipose tissue expansion.
Rachel David- Copyright © 2012 Nature Publishing Group, a division of Macmillan Publishers Limited; used with permission
ORIGINAL RESEARCH PAPER
Tran, K. V. et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells.
Cell Metab. 15, 222-229 (2012).