Introduction. Ghrelin is a gastrointestinal endocrine peptide that was initially identified as the endogenous ligand of growth hormone secretagogue receptor; however, recently, the cardiovascular effect of this peptide has been indicated. In this study, we investigated the effect of ghrelin administration on serum biomarkers of angiogenesis including leptin, nitric oxide (NO), vascular endothelial growth factor (VEGF), and its soluble receptor (VEGF receptor 1 or sFlt-1) in control- and diet-induced obese mice. Methods. Male C57BL/6 mice were randomly divided into four groups, normal diet (ND) or control, ND + ghrelin, high-fat-diet (HFD) or obese and HFD + ghrelin ( /group). Obese and control groups received either HFD or ND for 15 weeks. Then, the ghrelin was injected subcutaneously 100？μg/kg twice daily for 10 days. At the end of experiment, blood samples were collected for blood glucose, serum insulin, VEGF, sFlt-1, NO, and leptin measurements. Results. The obese animals had higher serum NO and leptin concentrations without changes in serum VEGF and sFlt-1 levels compared to control. Administration of ghrelin significantly increased serum VEGF and decreased serum leptin and NO concentrations in HFD group. Conclusion. Since ghrelin changes serum biomarkers of angiogenesis, it seems that it gets involved during states with abnormal angiogenesis. 1. Introduction Prolonged imbalance of caloric intake and energy expenditure leads to complex metabolic disorder of obesity. It is associated with most common and chronic human diseases including type 2 diabetes, heart diseases, hypertension, and cancer [1]. Angiogenesis, the formation of new blood vessels from preexisting ones, is tightly linked with adipogenesis [2] and is considered as an essential component in development and expansion of adipose tissue [3]. Since expansion of adipose tissue (increasing cell size and number) creates adipose tissue hypoxia, it can lead to stabilization of the transcription factor hypoxia inducible factor1α (HIF-1α) [4, 5] that induces an angiogenic response [6]. Ghrelin is a gastrointestinal endocrine peptide and is identified as an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R Ia) [7]; however, it also regulates food intake and is associated with obesity [8]. Ghrelin and its receptors are expressed in endothelial cells and stimulate endothelial cell proliferation, migration, and angiogenesis [9]. Recently, the impact of ghrelin on cardiovascular system has been reported [10] including a decrease of peripheral vascular resistance in
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