Abstract 457: Constitutive Expression of Fibroblast Growth Factor 1 in Endothelial Cells Alters Adipose Tissue Development
The development of healthy adipose tissue is dependent on both adipogenesis and angiogenesis. Resident endothelial and adipogenic cells within the growing depot produce angiogenic factors that stimulate angiogenesis in order to provide vascular support for the metabolic demands of the tissue. Since endothelial cells also produce adipokines that promote fat cell maturation, depots with higher vascular density tend to have more numerous, but smaller adipocytes than those with fewer vessels. Although the risk for the development of insulin resistance syndromes and cardiovascular disease is significantly higher in individuals with hypertrophic obesity - a condition characterized by the presence of enlarged and poorly vascularized adipocytes - the molecular mechanisms governing communication between adipogenic and endothelial cell populations within an adipose depot are poorly characterized. Acidic Fibroblast Growth Factor (FGF1) is an angiokine secreted by both adipocytes and endothelial cells and has also been reported to stimulate the production of adipocytes. To test the role of FGF1 in adipose tissue development, we analyzed weight gain, blood glucose, adipogenic hormone levels and fat tissue morphology in control and genetically-manipulated mice constitutively expressing an endothelial-specific FGF1 transgene. For these studies, mice were fed a high-fat, “Western” diet over the course of fourteen weeks. We found that a subpopulation of the FGF1-transgenic animals displayed significant differences in weight gain, fat cell size and hormone levels in comparison to control animals. Interestingly, the fat depots from the leanest animals also appeared to contain more “brown fat” than those taken from the more obese individuals. These results suggest that FGF1 may be a critical mediator in maintaining the balance between adipocyte number, size and vessel density within adipose depots. Since obesity is a health crisis in the United States, these studies may contribute to the development of therapeutic agents used to treat pathological conditions associated with abnormal weight gain.
- © 2012 by American Heart Association, Inc.