Article

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: 31.48). 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, Aug 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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    • "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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    • "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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