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      An Evaluation of Acylated Ghrelin and Obestatin Levels in Childhood Obesity and Their Association with Insulin Resistance, Metabolic Syndrome, and Oxidative Stress

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          Abstract

          Background: Ghrelin is a 28-amino acid peptide with an orexigenic property, which is predominantly produced by the stomach. Acylated ghrelin is the active form of this hormone. Obestatin is a 23-amino acid peptide which is produced by post-translational modification of a protein precursor that also produces ghrelin. Obestatin has the opposite effect of ghrelin on food intake. The aim of this study was to evaluate acylated ghrelin and obestatin levels and their ratio in obese and normal-weight children and adolescents, and their association with metabolic syndrome (MetS) parameters. Methods: Serum acyl-ghrelin, obestatin, leptin, insulin, fasting plasma glucose (FPG), lipid profile, and malondialdehyde (MDA) were evaluated in 73 children and adolescents (42 obese and 31 control). Insulin resistance was calculated by a homeostasis model assessment of insulin resistance (HOMA-IR). MetS was determined according to IDF criteria. Results: Acyl-ghrelin levels were significantly lower in obese subjects compared to the control group and lower in obese children with MetS compared to obese subjects without MetS. Obestatin was significantly higher in obese subjects compared to that of the control, but it did not differ significantly among those with or without MetS. Acyl-ghrelin to obestatin ratio was significantly lower in obese subjects compared to that in normal subjects. Acyl-ghrelin showed significant negative and obestatin showed significant positive correlations with body mass index (BMI), BMI Z-score, leptin, insulin, and HOMA-IR. Acyl-ghrelin had a significant negative correlation with MDA as an index of oxidative stress. Conclusion: Ghrelin is decreased and obestatin is elevated in obesity. Both of these hormones are associated with insulin resistance, and ghrelin is associated with oxidative stress. The balance between ghrelin and obestatin seems to be disturbed in obesity.

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          Childhood obesity and adult morbidities.

          The prevalence and severity of obesity have increased in recent years, likely the result of complex interactions between genes, dietary intake, physical activity, and the environment. The expression of genes favoring the storage of excess calories as fat, which have been selected for over many millennia and are relatively static, has become maladaptive in a rapidly changing environment that minimizes opportunities for energy expenditure and maximizes opportunities for energy intake. The consequences of childhood and adolescent obesity include earlier puberty and menarche in girls, type 2 diabetes and increased incidence of the metabolic syndrome in youth and adults, and obesity in adulthood. These changes are associated with cardiovascular disease as well as with several cancers in adults, likely through insulin resistance and production of inflammatory cytokines. Although concerns have arisen regarding environmental exposures, there have been no formal expert recommendations. Currently, the most important factors underlying the obesity epidemic are the current opportunities for energy intake coupled with limited energy expenditure.
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            The metabolic syndrome in children and adolescents.

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              Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.

              Ghrelin, a circulating appetite-inducing hormone, is derived from a prohormone by posttranslational processing. On the basis of the bioinformatic prediction that another peptide also derived from proghrelin exists, we isolated a hormone from rat stomach and named it obestatin-a contraction of obese, from the Latin "obedere," meaning to devour, and "statin," denoting suppression. Contrary to the appetite-stimulating effects of ghrelin, treatment of rats with obestatin suppressed food intake, inhibited jejunal contraction, and decreased body-weight gain. Obestatin bound to the orphan G protein-coupled receptor GPR39. Thus, two peptide hormones with opposing action in weight regulation are derived from the same ghrelin gene. After differential modification, these hormones activate distinct receptors.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                23 June 2016
                July 2016
                : 5
                : 7
                : 61
                Affiliations
                [1 ]Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular–Cellular Sciences Institute, Tehran University of Medical Sciences, 1411715851 Tehran, Iran; mrazar@ 123456tums.ac.ir
                [2 ]H. Aliasghar Hospital, Iran University of Medical Sciences, 1449614535 Tehran, Iran; a_p_808@ 123456yahoo.com (A.P.); dr.mnrbh@ 123456yahoo.com (M.N.)
                [3 ]Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, 1449614535 Tehran, Iran; dara1khosravi@ 123456gmail.com
                [4 ]Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, 1417614418 Tehran, Iran; ildavod@ 123456yahoo.com
                Author notes
                [* ]Correspondence: Nourbakhsh.m@ 123456iums.ac.ir ; Tel.: +98-21-8670-3109
                Article
                jcm-05-00061
                10.3390/jcm5070061
                4961992
                27348010
                c7d3bf0e-c12a-46e7-977f-b37f387ad65b
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 April 2016
                : 01 June 2016
                Categories
                Article

                ghrelin,obestatin,obesity,insulin resistance,metabolic syndrome,oxidative stress

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