Systemic Ghrelin Administration Alters Serum Biomarkers of Angiogenesis in Diet-Induced Obese Mice

Abstract

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 (n = 6/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.

Antiobesity and Hypolipidemic Activity ofMoringa oleiferaLeaves against High Fat Diet-Induced Obesity in Rats

“…A streak of evidence indicates that serotonin, histamine, dopamine, and their associated receptor activities are closely associated with obesity regulation [5]. Most importantly, strong evidences are available that elicited the role of leptin, ghrelin, and neuropeptides in obesity [12][13][14]. Currently, no pharmacological treatment provides sustained weight loss with minimal adverse effects [15,16].…”

Ghrelin

“…A recent study in a rat model of cardiopulmonary bypass (CPB) shows that ghrelin treatment reduces inflammatory responses, apoptosis and oxidative stress induced by CPB, and preserves the cardiac pumping function through GHS-R1a and Akt signaling (15). Increased angiogenesis is measured by changes in vascular endothelial growth factor (VEGF), VEGF receptor, and nitric oxide (NO) (45). Ghrelin treatment in rat model of MI demonstrates increased VEGF expression and angiogenesis (16).…”

“…Ghrelin treatment in rat model of MI demonstrates increased VEGF expression and angiogenesis (16). In diet-induced obese mice, systemic ghrelin treatment increases serum VEGF, and decreases NO concentrations (45). Overall, ghrelin treatment may reduce CSNA inflammation and oxidative stress in the heart, and induce angiogenesis.…”

Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

“…Of note, in the present study, 3‐week high‐dose ghrelin treatment significantly inhibited the plasma VEGF‐A levels compared with low‐dose ghrelin. However, it might remain to be seen whether ghrelin can regulate the VEGF system, because some studies reported that ghrelin promoted the VEGF system, in contrast, and inhibited the levels . Further study may be needed to establish the detailed meaning of the evaluation and regulation of circulating VEGF levels.…”