Ghrelin did not change coronary angiogenesis in diet-induced obese mice.

Ghrelin is a 28 amino acids peptide that initially was recognized as an endogenous ligand for growth hormone secretagogue receptor (GHSR). Recently, a number of studies demonstrated that ghrelin is a cardiovascular hormone with a series cardiovascular effect. The main objective of this study was to investigate the effect of systemic ghrelin administration on angiogenesis in the heart and its correlation with serum leptin levels in normal and diet-induced obese mice. 24 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 HFD or ND, respectively, for 14 weeks. Then, the ghrelin was injected subcutaneously 100µg/kg twice daily. After 10 days, the animals were sacrificed, blood samples were taken and the hearts were removed. The angiogenic response in the heart was assessed by immunohisochemical staining. HFD significantly increased angiogenesis in the heart expressed as the number of CD31 positive cells than standard diet. Ghrelin did not alter angiogenesis in the heart in both obese and control groups, however, it reduced serum nitric oxide (NO) and leptin levels in obese mice. There was a strong positive correlation between the number of CD31 positive cells and serum leptin concentration (r=0.74). Leptin as an angiogenic factor has a positive correlation with angiogenesis in the heart. Although systemic administration of ghrelin reduced serum leptin and NO levels in obese mice, however, it could not alter coronary angiogenesis.

Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma in obese mice.

BACKGROUND: Notch is a signaling molecule which plays a role in angiogenesis and γ-secretase is required for processing of Notch. In this study, we investigated the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice. METHODS: 18 mice were divided into three groups; control, obese (diet-induced) and obese+DAPT. After 15 weeks, the obese mice were subjected for tumor induction of CT26 colon adenocarcinoma cells (5 x 105 cells). When the tumor size reached approximately 350 ± 50 mm3, half of the obese animals received DAPT (10mg/kg/day) subcutaneously. Blood samples were taken after 14 days and the tumors harvested for immunohistochemical staining and capillary density were reported as CD31 positive cells/mm2. RESULTS: The obese animals had higher serum leptin and NO concentrations, while, serum VEGF and VEGFR-1 concentrations were not different compare to control group. Administration of DAPT in obese mice significantly reduced serum VEGFR-1 and leptin concentrations and increased serum NO level (p < 0.05). Capillary density in the tumors of obese animals was not different compare to control groups. DAPT administration could not alter capillary density in the tumors. CONCLUSION: Administration of DAPT in obese mice altered serum angiogenic factors, however, it could not modulate tumor angiogenesis in diet-induced obese mice (Fig. 4, Ref. 26).

Systemic administration of ghrelin did not restore angiogenesis in hindlimb ischemia in control and diet-induced obese mice.

BACKGROUND: Ghrelin is a novel growth hormone releasing peptide that mainly regulates food intake and energy homeostasis, however, recently, it is indicated that it may be closely related with physiological and/or pathological angiogenesis. OBJECTIVES: The objective of the present study was to evaluate the effect of systemic ghrelin administration on angiogenesis in hindlimb ischemia in normal and diet-induced obese mice. METHODS: 24 male C57BL/6 mice were fed with high-fat diet (HFD) or standard for 14 weeks. Then, the mice underwent unilateral hindlimb ischemia. Next, each group was divided into the two subgroups: treatment with ghrelin (100 µg/kg, twice daily, Sc) or without treatment. After 10 days, the animals were sacrificed, blood samples were taken and the gastrocnemius muscles removed. RESULTS: There was no significant difference in capillary/fiber ratio in hind limb ischemia between obese and control groups. Administration of ghrelin reduced serum nitric oxide (NO) and leptin and increased vascular endothelial growth factor (VEGF) concentrations in obese mice, however, did not change the capillary/fiber ratio in ischemic legs. CONCLUSION: Systemic administration of ghrelin did not restore angiogenesis in hindlimb ischemia in control and diet-induced obese mice (Fig. 4, Ref. 35).

Changes of serum angiogenic biomarkers and their correlations with serum leptin concentration.

AIM: Obesity is considered as a major health problem. Angiogenic vessels by providing oxygen, nutrients and growth factors trigger growth and survival signals in adipocytes. We aimed to investigate the effect of high-fat diet (HFD) on serum angiogenic biomarkers including vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR1), nitric oxide (NO) concentrations and their correlations with serum leptin level in obese and control groups. METHODS: Twenty male C57BL/6 mice were randomly assigned into the control and obese groups. Obese group received HFD for 15 weeks. At the end of experiment, blood samples were collected for blood glucose, serum insulin, VEGF, sVEGFR1, NO and leptin level measurements and correlation between serum angiogenic factors and leptin levels were analyzed. RESULTS: HFD induced higher serum NO and leptin levels compared to the control group, while, it did not affect serum VEGF and sVEGFR1 concentrations. There was a strong positive correlation between serum leptin and NO levels (r=0.78), however, a weak correlation was found between serum leptin and VEGF and VEGFR-1 concentrations. CONCLUSION: It seems that the angiogenic activities in obese mice are through the mechanisms that were not regulated by VEGF or VEGF receptors rather; other factors such as leptin and NO are involved (Tab. 1, Fig. 4, Ref. 32).

Systemic ghrelin administration alters serum biomarkers of angiogenesis in diet-induced obese mice.

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.