Proceedings of the National Academy of Sciences · 2002 · 829 citations · 37 references
MedicineOncologyPharmacologyMetabolic RegulationTumor MicroenvironmentTumor ProgressionAdipose TissueAngiogenesisAngiogenesis In CancerCancer MetabolismWeight LossWeight ManagementAdipose Tissue AngiogenesisAdipose Tissue RemodelingEndothelial ProliferationRemodelingTissue GrowthTissue Growth RegulationVascular Endothelial Growth Factor InhibitorsVascular Remodeling
Angiogenesis is essential for tumor growth. The study tested whether adipose tissue expansion also requires neovascularization. Researchers treated mice from various obesity models with anti‑angiogenic agents to assess effects on adipose tissue. Anti‑angiogenic therapy produced dose‑dependent, reversible weight loss and adipose depletion, accompanied by vascular remodeling, metabolic adjustments, and no adverse effects, showing adipose mass can be regulated by its vasculature.
Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.
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