Journal
INTEGRATIVE BIOLOGY
Volume 12, Issue 4, Pages 81-89Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intbio/zyaa006
Keywords
adipose tissue engineering; white adipose tissue; endothelial cells; vasculature; adipocyte; co-culture
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Funding
- MARC-U*Star Program, National Institutes of Health [T34 GM 087239]
- National Institute of Diabetes and Digestive and Kidney Diseases, Diabetic Complications Consortium [DK076169, DK115255]
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Central to the development of adipose tissue (AT) engineered models is the supporting vasculature. It is a key part of AT function and long-term maintenance, but the crosstalk between adipocytes and endothelial cells is not well understood. Here, we directly co-culture the two cell types at varying ratios in a 3D Type I collagen gel. Constructs were evaluated for adipocyte maturation and function and vascular network organization. Further, these constructs were treated with forskolin, a beta-adrenergic agonist, to stimulate lipolysis and browning. Adipocytes in co-cultures were found to be less mature than an adipocyte-only control, shown by smaller lipid droplets and downregulation of key adipocyte-related genes. The most extensive vascular network formation was found in the 1:1 co-culture, supported by vascular endothelial growth factor (VEGF) upregulation. After forskolin treatment, the presence of endothelial cells was shown to upregulate PPAR coactivator 1 alpha (PGC-1 alpha) and leptin, but not uncoupling protein 1 (UCP1), suggesting a specific crosstalk that enhances early stages of browning.
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