C4: Vascular control of adipose tissue and consequences for tumor progression
Adipose tissue is a highly vascularized metabolic and endocrine organ that is critically involved in the pathogenesis of metabolic diseases, tumor progression and metastasis of intra-abdominal tumors such as ovarian carcinoma. Expansion and shrinkage of white adipose tissue is accompanied by angiogenesis and vascular regression, respectively. Recent work has demonstrated that improvement of blood perfusion in adipose tissue leads to enhanced insulin sensitivity, reduced inflammation, browning of white adipose tissue and prevention of diet-induced obesity. Little is known regarding how the endothelium controls the biology of the adjacent cells in adipose tissue.
Our data indicate that endothelial Notch signaling restrains angiogenesis, controls the flux of fatty acids across the endothelium in muscle, and facilitates infiltration with myeloid immune cells in several tissues. Preliminary experiments indicate that endothelial Notch signaling also controls the flux of insulin across the endothelium and angiogenesis in various fat depots. As such this project will address how endothelial-specific manipulation of Notch signaling alters the vasculature within adipose tissue and how this will affect adipocytes and immune cells. This should lead to a better understanding about the vascular-driven control of adipose tissue biology in health, obesity and cancer metastasis.