Introduction: During nutrient excess, white adipose tissue undergoes expansive remodelling, which is critically dependent on new vessel development to provide oxygen and other nutrients. In advanced obesity the relationship between white adipose tissue expansion and neovascularisation becomes uncoupled leading to inadequate perfusion of adipose tissue, ischemia, cell death and inflammation. Under these circumstances the secretory profile of adipocytes becomes unfavourable. While obesity induced perturbations of insulin signalling have been extensively studied, a role for endothelial cell IGF-1 signalling in obesity and its complications is only beginning to emerge. A more complete understanding of the role of IGF-1 at the level of the endothelium in obesity may open new avenues to develop treatments for the vascular complications. Hypothesis: Reducing insulin like growth factor -1 receptor (IGF-1R) expression in the endothelium protects against obesity related insulin resistance and adverse adipose tissue remodelling. Methods and Results: To study the effects of IGF-1R deficiency on metabolic homeostasis and adipocyte biology we generated a tamoxifen inducible endothelial specific mouse with IGF1-R deficiency (ECIGF-1RKD). To induce obesity, mice received free access to a high fat diet (HFD) for either 2 weeks or 8 weeks. We first confirmed a reduction in IGF-1R expression by using the mTmG system and also by immunoblotting pulmonary endothelial cells from ECIGF-1RKD mice and control litter mates. There was no effect on baseline body mass, insulin sensitivity or glucose tolerance in ECIGF-1RKD mice compared with controls when fed a chow diet. However, after HFD, ECIGF-1RKD mice were more insulin sensitive, but glucose tolerance, fasting blood glucose and insulin levels, glucose stimulated insulin secretion, temperature, body mass and organ weights were no different. Histological examination showed that after HFD, ECIGF-1RKD mice had smaller white adipocytes, which expressed more uncoupling protein-1 and vascular endothelial growth factor when compared to controls. There was no difference in brown adipocytes of fatty liver. Finally, white adipose tissue from ECIGF-1RKD had enhanced endothelial sprouting and was more vascularised when stained with isolectin B4. Conclusion: Reducing endothelial cell IGF-1R enhances white adipose tissue angiogenesis and also leads to a favourable potentially anti-atherosclerotic metabolic profile. [ABSTRACT FROM AUTHOR]