Angiogenesis in an in vivo model of adipose tissue development

TLDR

Obesity elevates cardiovascular and cancer risk, and expanding adipose tissue is one of the few adult sites of active angiogenesis, yet mechanisms remain poorly understood due to a lack of quantitative model systems. The study investigates the angiogenic process during adipose tissue development using the 3T3‑F442A preadipocyte model. 3T3‑F442A preadipocytes were implanted subcutaneously into athymic Balb/c nude mice to generate developing fat pads. The implanted cells formed highly vascularized fat pads within 14–21 days that resembled normal subcutaneous adipose tissue, with microvasculature appearing by day 5 and parallel increases in endothelial and adipogenesis markers, indicating that neovascularization arises by sprouting from host vessels adjacent to nerves rather than from endothelial progenitor cells.

Abstract

Obesity is associated with an increased risk for cardiovascular disease and cancer. Angiogenesis is a critical component of these pathological processes, and expanding adipose tissue represents one of the few sites of active angiogenesis in the adult. Despite the potential importance of angiogenesis in obesity, little is known about underlying mechanisms. This problem is magnified by the absence of useful quantitative model systems. In this report, we examine the angiogenic process using the 3T3-F442A model of adipose tissue development. In this model, 3T3-F442A preadipocytes are implanted subcutaneously into athymic Balb/c nude mice. We show that these cells develop into highly vascularized fat pads over the next 14-21 days, and that these fat pads are morphologically similar to normal subcutaneous adipose tissue. Histological studies demonstrate that a new microvasculature is evident as early as 5 days after cell implantation, and real-time quantitative RT-PCR analyses show that the expression of endothelial cell markers and adipogenesis markers increase in parallel during fat pad development. Finally, these preliminary studies suggest that the neovasculature originates by sprouting from larger, host-derived blood vessels that run parallel to peripheral nerves and that endothelial progenitor cells play little, if any, role in this process.