Endothelial Cells: New Players in Obesity and Related Metabolic Disorders

ECs are the metabolic gatekeeper of the organism. EC dysfunction is an early event in the pathogenesis of obesity. Modulation of vessel function is sufficient to regulate systemic energy balance. Thus, blood vessels have become a promising target for overcoming metabolic perturbations associated with obesity. In rodent models, inhibition of angiogenesis is a good therapeutic strategy in pre-existing obesity. Conversely, enhanced vessel growth protects against early exposure to a high-fat diet and in already obese mice. Metabolic disorders such as obesity are accompanied by endothelial cell (EC) dysfunction and decreased vascular density. The current paradigm posits that metabolic alterations associated with obesity secondarily lead to EC dysfunction. However, in view of recent evidence reporting that EC dysfunction per se is able to cause metabolic dysregulation, this paradigm should be revisited and further elaborated. In this article we summarize current views and discuss evidence in favor of a causal role for ECs in systemic metabolic dysregulation. We also integrate and contextualize current research in a pathophysiological framework and discuss potential therapeutic strategies targeting angiogenesis to help to counteract obesity. Metabolic disorders such as obesity are accompanied by endothelial cell (EC) dysfunction and decreased vascular density. The current paradigm posits that metabolic alterations associated with obesity secondarily lead to EC dysfunction. However, in view of recent evidence reporting that EC dysfunction per se is able to cause metabolic dysregulation, this paradigm should be revisited and further elaborated. In this article we summarize current views and discuss evidence in favor of a causal role for ECs in systemic metabolic dysregulation. We also integrate and contextualize current research in a pathophysiological framework and discuss potential therapeutic strategies targeting angiogenesis to help to counteract obesity. generic term referring to cytokines and other proteins that are exclusively secreted by adipocytes and influence a range of organismal biological processes. a type of adipocyte that exhibits a phenotype intermediate between white fat cells (energy storage) and brown fat cells (thermogenesis). a biological process by which white adipocytes are converted from fat-storing cells to fat-burning (thermogenic) cells. cells of mesodermal origin which line the lumen of blood and lymphatic vessels. the relation between calories consumed and calories burned. oxygen deprivation. a category of signaling molecules released by immune cells that exert diverse immunoregulatory functions. a signaling gas mainly produced by ECs that regulates vascular tone and blood flow by activating guanylate cyclase in vascular smooth muscle. a chronic multifactorial disease in which excessive accumulation of fat results in adverse health consequences. Clinically, obesity in adults is defined as a body mass index (body mass divided by the square of the body height in kg/m2) of ≥30. imbalance between ROS production and antioxidant cellular defenses. a measure of the level of arterial or tissue oxygenation; it reflects the balance between oxygen delivery and consumption. highly reactive chemical compounds that contain oxygen. They are generated by diverse metabolic processes. At low concentrations ROS act as signaling molecules, but at higher concentrations cause macromolecular damage. the most prominent angiogenic cytokine.