33 research outputs found

    Ghrelin acylation by ghrelin-O-acyltransferase can occur in healthy part of oncologic liver in humans

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    INTRODUCTION: Activation of ghrelin is controlled by the enzyme Ghrelin-O-Acyl Transferase (GOAT). In humans, localization of this acylation is poorly understood. The aim of that study was to explore GOAT localization and activation in human Liver by evaluating both bioactive and non-bioactive ghrelin in the blood stream entering and leaving liver and to simultaneously evaluate GOAT mRNA expression in Liver. METHODS: Healthy part of oncologic hepatic tissue collected from nine patients undergoing hepatectomy was used to evaluate GOAT mRNA expression by quantitative real time polymerase chain reaction (RTqPCR). Simultaneously blood from portal vein, supra hepatic vein, sub clavicular vein and radial artery was also sampled to assay total and acylated ghrelin. RESULTS: Acylated ghrelin level was significantly increased in supra hepatic vein compared to portal vein level (385±42 ng/ml vs. 268±24 ng/ml, p=0.04). Supra hepatic vein to portal vein ratio for acylated ghrelin (acylation ratio) is at 1.4±0.1. Mean expression of GOAT mRNA in liver, expressed as 2-∆Ct/µg total RNA/1µl of liver tissue was at 0.042±0.021 arbitrary units. GOAT mRNA expression in liver was correlated with acylated to total ghrelin ratio in supra hepatic vein (p=0.016, R=0.75) and with acylation liver ratio (p=0.05, R=0.61). CONCLUSIONS: Blood concentration of acylated ghrelin was found significantly increased after its passage through liver suggesting acylation can occur in the liver. RTqPCR data confirmed the presence of GOAT in liver, with positive correlation between GOAT expression and acylated ghrelin liver ratio. This study strongly suggests that liver is a site of ghrelin acylation in human

    Ghrelin/obestatin ratio in twopopulations with low bodyweight: Constitutional thinness and anorexia nervosa: constitutional thinness and anorexia nervosa

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    International audienceConstitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients.Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects.Obestatin circadian levels were significantly higher in AN (p < 0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p < 0.05). The percentage of acylated ghrelin was found decreased in CT group (p < 0.05).The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition
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