Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake

Department of Obstetrics and Gynecology, Stanford University, Palo Alto, California, United States
Science (Impact Factor: 33.61). 12/2005; 310(5750):996-9. DOI: 10.1126/science.1117255
Source: PubMed

ABSTRACT 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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Available from: Pei-Gen Ren, Sep 25, 2015
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    • "Given the identified role of ghrelin in GH secretion and appetite stimulation, it was surprising when the ghrelin knockout (KO) mouse was reported to have no change in size, growth rate, food intake, body composition and behaviour compared to WT littermates (Sun et al. 2003). More recently there has been a focus on the role of multiple alternative products from the ghrelin gene (e.g., obestatin; Zhang et al. 2005), the role of unacetylated ghrelin (comprising 75% of circulating ghrelin) and non-endocrine roles of ghrelin in psychiatric disorders (Wittekind & Kluge 2015), tumour progression (Xu et al. 2015), brain injury (Xie et al. 2015) and heart failure (Khatib et al. 2014). Like the multifunctional SST, ghrelin, initially a GHS, is now recognised as a pleiotropic hormone. "
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    ABSTRACT: At the time of the publication of Geoffrey Harris's monograph on 'Neural Control of the Pituitary Gland' 60 years ago, the pituitary was recognised to produce a growth factor and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the growth hormone (GH) axis has included identification of the key central components of the GH axis - GHRH and somatostatin in the 1970's and 80's - and in the 1990's ghrelin. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980's and 90's; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses has been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As understanding of the control of growth hormone secretion advanced, so developments of treatments for GH axis disorders have evolved. Administration of pituitary derived human growth hormone was followed by the introduction of recombinant human growth hormone in the 1980's, and more recently long-acting GH preparations. For growth hormone excess disorders, firstly dopamine agonists were used followed by somatostatin analogues and in 2005 the introduction of the GH receptor blocker pegvisomant. This review will cover the evolution of these discoveries, and build a picture of our current understanding the hypothalamo-growth hormone axis.
    Journal of Endocrinology 06/2015; DOI:10.1530/JOE-15-0120 · 3.72 Impact Factor
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    • "A signal transduction pathway or even the cellular receptors for obestatin are still unknown. Discoverers of obestatin, Zhang et al. (2005) have proposed that this polypeptide exerts its biological effects by binding to the G protein-coupled receptor 39 (GPR39). However, later studies have showed that GPR39 is not the obestatin receptor (Holst et al., 2007). "
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    ABSTRACT: Obestatin, as ghrelin, has been originally extracted from the stomach, which remains its major source. Previous studies have shown that administration of obestatin exhibits protective and healing-promoting effects in several organs, including the stomach and kidney. In pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis and promotes survival of pancreatic beta cells and human islets. The aim of the present study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16nmol/kg/dose) was administered intraperitoneally twice: 0.5h before exposure to ischemia, and 3h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion, and included histological, functional, and biochemical analyses. Treatment with obestatin reduced morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland. These effects were accompanied by an improvement of pancreatic DNA synthesis and superoxide dismutase activity, and a decrease in serum level of lipase and pro-inflammatory interleukin-1β. Moreover pretreatment with obestatin reduced myeloperoxidase activity and malondialdehyde concentration in pancreatic tissue of rats with acute pancreatitis. Administration of obestatin inhibits the development of ischemia/reperfusion-induced acute pancreatitis. This observation, taken together with previous findings that obestatin protects the pancreas against cerulein-induced pancreatitis, indicates that protective effect of obestatin in the pancreas is universal and independent of the primary cause of acute pancreatitis. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 04/2015; 760. DOI:10.1016/j.ejphar.2015.04.016 · 2.53 Impact Factor
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    • "We also predict that falcons do not produce the preproghrelin-derived peptide obestatin. Obestatin has a number of functions in mammals (Seim et al., 2011), however , although it was originally thought to suppress ghrelin-stimulated appetite in mammals (Zhang et al., 2005), it is now widely accepted that it does not play a role in appetite regulation (Seim et al., 2011). Similarly, in the domestic chicken, obestatin does not appear to have effects on food intake and it did not affect gut motility (Song et al., 2012). "
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    ABSTRACT: Ghrelin and leptin are the only known peripherally secreted appetite-regulating hormones of vertebrates. Here we consider the ghrelin gene (GHRL) of birds (class Aves), where it has been reported that ghrelin inhibits rather than augments feeding. Thirty-one bird species were compared, revealing that most species harbour a functional copy of GHRL and the coding region for its derived peptides ghrelin and obestatin. We provide evidence for loss of GHRL in saker and peregrine falcons, and this is likely to result from the insertion of an ERVK retrotransposon in intron 0.We hypothesise that the loss of anorexigenic ghrelin is a predatory adaptation that results in increased food-seeking behaviour and feeding in falcons. Copyright © 2014. Published by Elsevier Inc.
    General and Comparative Endocrinology 12/2014; 216. DOI:10.1016/j.ygcen.2014.11.016 · 2.47 Impact Factor
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