Obestatin; anabolic and restores testicular function!

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    Obestatin; anabolic and restores testicular function!


    Obestatin is a gastric peptied that is related to grelin and was initially reported to be involved in decreased food intake makeing it useful as a anti obesity compound... these findings have been refuted by a few recent studies but not clearly disproved. Besides being highly regenerative to muscle cells recent research show that obestatin is involved in inhibiting thirst and anxiety, improving memory, regulating sleep, positively affecting cell migration, proliferation and differentiation, increasing insulin sensitivity, improving testicular function, fighting fatty liver, being a vaso relaxant, cardio protectant, and increasing the secretion of pancreatic enzymes. Who knows what other positive benefits Obestatin may posses. To me I certainly seems it could be utilized by the bodybuilding and athletic cummunities in a number of interesting ways. Namely PCT. It seems to rejuvenate many tissues besides muscle! Heart, liver, testis, pancreas, and the vascular system! That's pretty cool In my view. I don't think some athletes really realize how much stress we put out bodies through to achieve the extreme results we desire. Anything that can further our progression toward these goals and at the same time fight the bodily damage that come with that progress is a major find!

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    Small peptide for muscle regeneration
    University of Santiago de Compostela
    posted on 08/28/2012
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    We have found that the small peptide obestatin acts as a myogenic regenerator system. We have shown that this peptide is useful for inducing muscle regeneration, and thus for the treatment of injuries or diseases associated with muscle damage, such as myopathies, muscle necrosis, muscle atrophy and muscular dystrophy.

    SUGGESTED USES
    Potential use as a therapeutic agent for the treatment of trauma-induced muscle injuries or skeletal muscle myopathies, such as muscular distrophy and muscular atrophy

    ADVANTAGES
    Obestatin is a small peptide (23 aminoacids)
    Our experimental data show the effectiveness of obestatin as a muscle regenerative agent after muscle injury both in vitro and in vivo. Exogenous administration of obestatin in an animal model of muscle injury shows to accelerate muscle regeneration displaying an hypertrophic effect.
    Identification of the bioactive center of obestatin, that is, the minimal sequence that is determinant for its regenerative activity, is possible. This would allow to obtain new obestatin analogs with improved bioavailability, reducing the possible toxicity and side effects.

    INNOVATION DETAILS

    DETAILED DESCRIPTION
    The research team has identified the obestatin/GPR39 system as a relevant component of muscle regeneration, in which obestatin controls the myogenic differentiation program.

    The myogenic activity of obestatin was shown in vitro and in vivo. In vivo administration of obestatin upon muscle injury was shown to activate the expression of myogenic factors in the skeletal muscle and to produce muscle hypertrophy. In vitro, it promoted migration, proliferation and differentiation of myoblasts, three processes that are essential for muscle regeneration. Its administration promoted the exit of the cell cycle, the expression of myogenic transcription factors, the migration/invasion of myoblasts (increase of the differentiation index) and the fusion of myoblasts (increase in the fusion index) in order to determine the myotubes

    RESULTS
    THE MYOGENIC ACTIVITY OF OBESTATIN HAS BEEN SHOWN IN VITRO AND IN VIVO
    IN VIVO ASSAYS

    Exogenous administration of obestatin in an animal model of muscle injury shows to accelerate muscle regeneration displaying a hypertrophic effect. Chronic subcutaneus administration (24h, 72h) of obestatin in rats with induced muscle injury:
    • Activates the expression of myogenic factors in the skeletal muscle (MyoD, Myf5, Myf6, Pax-7,myogenin and MHC)
    • Produces muscle hypertrophy.
    Further in vivo tests included injections in mice at 24h intervals after muscle injury, as well as assays in as a model of sciatic denervation (Unpublished results).
    IN VITRO ASSAYS

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor are expressed in rat skeletal muscle and are up-regulated upon experimental injury.
    Obestatin promotes migration, proliferation and differentiation of myoblasts, three processes that are essential for muscle regeneration. Its administration promoted the exit of the cell cycle, the expression of myogenic transcription factors, the migration of myoblasts and the fusion of myoblasts in order to determine the myotubes. In vitro assays showed that obestatin:
    • Promotes myogenesis through the expression of myogenin and MHC (Myosin Skeletal Heavy Chain) on a dosis-dependent manner in rat L6E9 myoblasts.
    • Acivates the main mitogenic and myogenic factors (Akt, p38, pERK) in both L6E9 myoblasts and myotubes.
    • Induces an increase in the cell number of myoblasts at 48h after stimulation.
    • Promotes differentiation of myoblasts (Increases 2.5 times the differentiation index respect to control) as well as the fusion of myoblasts in order to determine the myotubes (increase in the fusion index: 20% (control) versus 70% (+obestatin) of myotubes with >4 nucleus)
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    Obestatin induces testosterone secretion from rat testis
    in vitro

    Hizbullah, Sarwat Jahan* and Shakeel Ahmed
    Reproductive physiology lab, Department of Animal sciences Quaid-i-Azam University, Islamabad. Pakistan.
    Accepted 10 March, 2011
    In this study, the effect of obestatin (23 amino acid peptide) on testosterone secretion in vitro, in the rat testis was observed. For this purpose, two different doses of obestatin (10-9 M and 10-8 M) were used alone and in combination with human chorionic gonadotropin (hCG) in fasting and fed conditions in two age groups. Fasting induced a significant reduction in body weight (p < 0.05) and plasma testosterone concentrations (0.001). hCG stimulated testosterone secretions were significantly (p < 0.05) high as compared to the basal control testosterone concentrations after 90 min in some groups and 180 min of incubation in all groups. Obestatin at the dose of 10-9 M alone and in combination with hCG failed to change testosterone concentrations in all groups; however, 10-8 M obestatin significantly (p < 0.05) induced hCG stimulated testosterone concentrations in both normally fed pre-pubertal and adult rats. No significant difference was noticed in 48 h fasted groups. This data suggests that, obestatin is a positive modulator of testosterone secretion and its effect depends upon the nutritional status of the body.
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    Possible Modulation of Testosterone Secretion by Obestatin in Pubertal Male Rats
    Sarwat Jahan*, Shakeel Ahmed, Nazifa Taqvim and Hizbullah
    Reproductive Physiology Lab, Department of Animal Sciences, Quaid-i-AzamUniversity, Islamabad.

    Abstract.- The objective of the present study was to examine the effect of different doses of obestatin on testosterone secretion in pubertal male Sprague Dawley rats. Animals were divided into three groups. One group served as control and the other two groups were treated with 8 and 16 nmol/kg of obestatin, respectively. Prior to sample collection, teflon cannula was implanted in lateral tail vein of rat and the sequential blood samples were collected 10 min before, at the time of obestatin treatment (0 min) and then at 10 min intervals upto 40 min. in heparinized syringes. The whole sampling was carried out under diethyl ether anesthesia. Plasma testosterone levels were determined by using Enzyme Immunoassay (EIA). Administration of obestatin (8 nmol/kg) in animals resulted in a significant (p<0.05) increase in mean plasma testosterone concentrations at 10 and 20 min after obestatin administration. Highly significant (p<0.001) increase in testosterone concentrations were observed at 30 min which then declined at 40 min. At dose of 16 nmol/kg in pubertal animals, a significant increase (p<0.05) was noticed in testosterone secretion at 20 and at 30 min after obestatin administration. Plasma testosterone concentrations then declined after 40 min. The present study suggests that this peptide may be involved in the regulation of testosterone secretion in pubertal male rats.
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    Effect of obestatin on morphometry of testes and testosterone secretion in male rats
    Sarwat Jahan*, Tabinda Sidrat, Shakeel Ahmed, Hizbullah Wazir and Kamran Ullah
    Reproductive physiology Laboratory, Department of Animal sciences Quaid-i-Azam University, Islamabad, Pakistan.
    Accepted 4 April, 2011
    This study was designed to evaluate the effects of chronic intra peritoneal administration of obestatin on plasma testosterone concentrations and cellular morphometry of the testes in male Sprague Dawly rats. The treatment groups were injected with obestatin (1 nmol/100 μl saline i.p), while the control groups received saline (100 μl i.p) for ten consecutive days. Blood samples were collected at day 1 and 10 during the dose administration and day 5 and 15 after the dose administration. All the samples were collected at 10:00 a.m. Testes were removed after sacrificing the rats on days 5 and 15 after the last injection. Plasma testosterone concentrations were found significantly high (p < 0.05) in the obestatin treated groups when compared with the control groups. Testicular histomorphometry revealed that, obestatin treatment caused a significant increase in the primary spermatocytes (P < 0.0001), secondary spermatocytes and spermatids (P < 0.005) and leydig cells population (p < 0.0001) both after 5 and 15 days. These findings indicated that obestatin can be a stimulator of testicular functions.
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    Obestatin induces testosterone but not prolactin secretion in male rat.
    Authors
    Sarwat Jahan; Shakeel Ahmed; Nazifa Taqvim; Hizbullah
    Journal
    Pakistan Journal of Zoology 2010 Vol. 42 No. 6 pp. 836-839
    ISSN
    0030-9923
    Record Number
    20113296484
    Abstract
    The present study was designed to investigate the in vivo effect of an anorexigenic gut peptide obestatin on plasma testosterone and prolactin secretion, in adult male Sprauge Dawley rats. One group of animals served as control (n=5), while the treatment group (n=5) received a single i.v. dose of 8 nmol/Kg of obestatin. Blood samples (200 l-250 l) were collected at -10, 0, 10, 20, 30 and 40 min of treatment. In treated group obestatin caused a significant (p<0.05) increase in plasma testosterone concentrations at 20 minutes. However, at 30 and 40 min post treatment, the plasma testosterone concentrations declined to non-significantly (P>0.05) higher values. A significant (P<0.05) increase in plasma testosterone concentrations was observed after treatment, compared to that before treatment. Obestatin showed no profound effect on plasma prolactin concentration in all the treated groups. It was concluded that obestatin i.v infusion leads to increase in plasma testosterone in adult male rats and may thus be involved in testosterone secretion, however, it has no effect on the prolactin secretion.
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    Improves pancreatic function


    Obestatin improves in vitro generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non differentiated cells

    A Baragli, C Grande, M Taliano, F Settanni, E Ghigo &; R Granta

    Author affiliations
    Introduction: The ghrelin gene products ghrelin and obestatin (Ob) protect mice from STZ-induced β-cell death, inflammation and STZ-induced diabetes. A possible event is ghrelin/Ob-induced regeneration of damaged β-cell population through the recruitment of pancreatic progenitor cells (PPC). We hypothesized that Ob affects proliferation and endocrine commitment of PPC within the islets of Langerhans.

    Methods: Islets of Langerhans were isolated from pancreas of 6 months old mice and plated for enrichment. Enriched islets were cultured to permit adhesion and stimulate islet-derived cell proliferation (emersion phase). Part of these islets were chronically treated with 100 nM Ob. After a week, culture medium was changed into a serum-free medium supplemented with leukaemia inhibitory factor and fibroblast growth factor 2 to allow proliferation of undifferentiated cells. The expression of staminal and endocrine markers was studied for the next 15 days. During this period cells proliferated (proliferation phase) and aggregated into islet-like cell clusters (ILCC) (differentiation phase).

    Results: During the emersion phase Ob treatment increased proliferation of β-cells, but not that of α-cells and of cells expressing Nestin, Ngn3, PDX1, Oct4. At the end of the proliferation phase, Ob-treated cells expressing Nestin or Oct4 highly proliferated, while cells clustering into ILCC expressed more Ngn3 with respect to control. At the end of the differentiation phase Ob-ILCC expressed higher levels of insulin and glucagon. Furthermore, glucose-induced insulin release was increased. Ob effect depended on its modulation of specific signalling molecules essential to endocrine pancreas development.

    Conclusions: Ob efficiently stimulated islet-derived cell proliferation and precursor cell differentiation into novel insulin and glucagon secreting ILCC. Thus, in vivo, Ob might ameliorate diabetic conditions through stimulation of PPC. Ob may also improve in vitro islet generation for transplantation purpose.
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    Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas.

    AuthorsEgido EM, et al. Show all Journal
    Regul Pept. 2009 Jan 8;152(1-3):61-6. doi: 10.1016/j.regpep.2008.08.003. Epub 2008 Aug 19.

    Affiliation
    Department of Physiology, Medical School, Universidad Autnoma de Madrid, San Martn de Porres 4, 28035 Madrid, Spain.
    Abstract
    Obestatin is a 23-amino acid peptide derived from preproghrelin, purified from stomach extracts and detected in peripheral plasma. In contrast to ghrelin, obestatin has been reported to inhibit appetite and gastric motility. However, these effects have not been confirmed by some groups. Obestatin was originally proposed to be the ligand for GPR39, a receptor related to the ghrelin receptor subfamily, but this remains controversial. Obestatin and GPR39 are expressed in several tissues, including pancreas. We have investigated the effect of obestatin on islet cell secretion in the perfused rat pancreas. Obestatin, at 10 nM, inhibited glucose-induced insulin secretion, while at 1 nM, it potentiated the insulin response to glucose, arginine and tolbutamide. The potentiated effect of obestatin on glucose-induced insulin output was not observed in the presence of diazoxide, an agent that activates ATP-dependent K(+) channels, thus suggesting that these channels might be sensitive to this peptide. Obestatin failed to significantly modify the glucagon and somatostatin responses to arginine, indicating that its stimulation of insulin output is not mediated by an alpha- or delta-cell paracrine effect. Our results allow us to speculate about a role of obestatin in the control of beta-cell secretion. Furthermore, as an insulinotropic agent, its potential antidiabetic effect may be worthy of investigation.
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    Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation

    Abstract: The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions.
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    Effect of obestatin on body weight, serum glucose and insulin levels in albino rats

    SUMMARY
    Obestatin, a peptide encoded by the ghrelin precursor gene, is said to exert ac- tions opposite to that of ghrelin. While ghrelin is said to increase appetite and de- crease energy expenditure, thus causing weight gain, obestatin acts like an anorexic hormone, decreasing appetite and reducing body weight gain, besides other effects such as reducing serum insulin and glucose levels. However, these actions have been submitted to serious contests with many la- boratories opposing each others’ argu- ments. In our studies on albino rats, obestatin was administered for two different periods of time. One group received intra- peritoneal obestatin for one week, while the other got it for two weeks. The control ani- mals received the vehicle alone. It was found that obestatin brought about a reduc- tion in the final body weight, while the con- trol rats continued to gain weight during the period of the experiments. The more the duration of administration of the hormone, more pronounced are the results. There was a fall in the serum glucose and insulin lev- els in the obestatin-treated rats in compari- son with the control rats. Therefore, it was concluded that the anti-obesity hormone obestatin decreases the food intake and the body weight by lessening the appetite in the experimental rats. The study may have implications for its use in obesity.
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    Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats.

    Abstract
    The ghrelin gene products, namely acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob), were shown to prevent pancreatic b-cell death and to improve b-cell function under treatment with cytokines, which are major cause of b-cell destruction in diabetes. Moreover, AG had been described previously to prevent streptozotocin (STZ)-induced diabetes in rats; however, the effect of either UAG or Ob has never been examined in this context. In the present study, we investigated the potential of UAG and Ob to increase islet b-cell mass and to reduce diabetes at adult age in STZ-treated neonatal rats. One-day-old rats were injected with STZ and subsequently administered with either AG, UAG or Ob for 7 days. On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. Similarly to AG, both UAG and Ob counteracted STZ-induced high glucose levels and improved plasma and pancreatic insulin levels, which were reduced by the diabetogenic compound. UAG and Ob increased islet area, islet number, and b-cell mass with respect to STZ treatment alone. Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. Taken together, our results suggest that in STZ-treated newborn rats, UAG and Ob improve glucose metabolism and preserve islet cell mass, granting a therapeutic potential in medical conditions associated with impaired b-cell function.
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    Regenerates heart tissue and improves function

    Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms.

    AuthorsAragno M, et al. Show all Journal
    Cardiovasc Diabetol. 2012 Oct 15;11:129. doi: 10.1186/1475-2840-11-129.

    Affiliation
    Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, Turin, 10125, Italy.

    Abstract
    BACKGROUND: The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats.

    METHODS: Diabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and -adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3 as well -1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR.

    RESULTS: OB preserved papillary muscle contractility (85 vs 27% of ND), -adrenergic response (103 vs 65% of ND), as well 1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3 phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium.

    CONCLUSIONS: OB displays a significant beneficial effect against the alterations of contractility and -adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of 1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3.
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    Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes.

    Authors: Alloatti G, et al.

    Affiliation
    Dipartimento di Biologia Animale e dell'Uomo, Via Accademia Albertina, 13, Torino 10123, Italy.

    Abstract
    Obestatin, a newly discovered peptide encoded by the ghrelin gene, induces the expression of genes regulating pancreatic beta-cell differentiation, insulin biosynthesis, and glucose metabolism. It also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase (PI3K) and ERK1/2 in pancreatic beta-cells and human islets. Since these kinases have been shown to protect against myocardial injury, we sought to investigate whether obestatin would exert cardioprotective effects. Both isolated perfused rat heart and cultured cardiomyocyte models of ischemia-reperfusion (I/R) were used to measure infarct size and cell apoptosis as end points of injury. The presence of specific obestatin receptors on cardiac cells as well as the signaling pathways underlying the obestatin effect were also studied. In the isolated heart, the addition of rat obestatin-(1-23) before ischemia reduced infarct size and contractile dysfunction in a concentration-dependent manner, whereas obestatin-(23-1), a synthetic analog with an inverse aminoacid sequence, was ineffective. The cardioprotective effect of obestatin-(1-23) was observed at concentrations of 10-50 nmol/l and was abolished by inhibiting PI3K or PKC by the addition of wortmannin (100 nmol/l) or chelerythrine, (5 micromol/l), respectively. In rat H9c2 cardiac cells or isolated ventricular myocytes subjected to I/R, 50 nmol/l obestatin-(1-23) reduced cardiomyocyte apoptosis and reduced caspase-3 activation; the antiapoptotic effect was blocked by the inhibition of PKC, PI3K, or ERK1/2 pathways. In keeping with these functional findings, radioreceptor binding results revealed the presence of specific high-affinity obestatin-binding sites, mainly localized on membranes of the ventricular myocardium and cardiomyocytes. Our data suggest that, by acting on specific receptors, obestatin-(1-23) activates PI3K, PKC-epsilon, PKC-delta, and ERK1/2 signaling and protects cardiac cells against myocardial injury and apoptosis induced by I/R.
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    Obestatin; potent vaso-relaxer(pumps) via N.O. activation!

    The gastrointestinal peptide obestatin induces vascular relaxation via specific activation of endothelium-dependent NO signalling.

    Authors: Agnew AJ, et al.

    Affiliation
    School of Biological Sciences, Queen's University Belfast, Belfast, UK.

    Abstract
    BACKGROUND AND PURPOSE: Obestatin is a recently discovered gastrointestinal peptide with established metabolic actions, which is linked to diabetes and may exert cardiovascular benefits. Here we aimed to investigate the specific effects of obestatin on vascular relaxation.

    EXPERIMENTAL APPROACH: Cumulative relaxation responses to obestatin peptides were assessed in rat isolated aorta and mesenteric artery (n≥ 8) in the presence and absence of selective inhibitors. Complementary studies were performed in cultured bovine aortic endothelial cells (BAEC).

    KEY RESULTS: Obestatin peptides elicited concentration-dependent relaxation in both aorta and mesenteric artery. Responses to full-length obestatin(1-23) were greater than those to obestatin(1-10) and obestatin(11-23). Obestatin(1-23)-induced relaxation was attenuated by endothelial denudation, l-NAME (NOS inhibitor), high extracellular K(+) , GDP-β-S (G-protein inhibitor), MDL-12,330A (adenylate cyclase inhibitor), wortmannin (PI3K inhibitor), KN-93 (CaMKII inhibitor), ODQ (guanylate cyclase inhibitor) and iberiotoxin (BK(Ca) blocker), suggesting that it is mediated by an endothelium-dependent NO signalling cascade involving an adenylate cyclase-linked GPCR, PI3K/PKB, Ca(2+) -dependent eNOS activation, soluble guanylate cyclase and modulation of vascular smooth muscle K(+) . Supporting data from BAEC indicated that nitrite production, intracellular Ca(2+) and PKB phosphorylation were increased after exposure to obestatin(1-23). Relaxations to obestatin(1-23) were unaltered by inhibitors of candidate endothelium-derived hyperpolarizing factors (EDHFs) and combined SK(Ca) /IK(Ca) blockade, suggesting that EDHF-mediated pathways were not involved.

    CONCLUSIONS AND IMPLICATIONS: Obestatin produces significant vascular relaxation via specific activation of endothelium-dependent NO signalling. These actions may be important in normal regulation of vascular function and are clearly relevant to diabetes, a condition characterized by endothelial dysfunction and cardiovascular complications.
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    Low Serum Concentration of Obestatin as a Predictor of Mortality in Maintenance Hemodialysis Patients

    Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes.
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    OBESTATIN ALLEVIATES INDOMETHACIN-INDUCED GASTRIC MUCOSAL INJURY VIA THE INHIBITION OF NEUTROPHIL RECRUITMENT
    Abstract number: PC263

    Memi1 Glsn, Semiha Sen2 Leyla, Nigar Ozdemir1 Zarife, Kiran3 Demir, Ercan3 Feriha, Yegen1 Berrak ., Yegen4 Cumhur

    1Department of Physiology, Marmara University School of Medicine, Istanbul
    2Siirt State Hospital, General Surgery Department, Siirt
    3Department of Histology and Embryology, Marmara University School of Medicine, Istanbul,
    4Department of General Surgery, Marmara University School of Medicine, Istanbul

    Objective:
    Obestatin, a 23-amino acid peptide derived from the ghrelin peptide precursor, is synthesized in the stomach. We have recently demonstrated the protective effect of obestatin in intestinal ischemia-reperfusion injury. We aimed to investigate the putative anti-ulcer and anti-oxidant effects of obestatin in a gastric ulcer model induced by a non-steroidal-anti-inflammatory drug.

    Methods:
    Sprague Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg; n=25) or vehicle (5% NaHCO3; n=5). Indomethacin-treatment was followed by either saline or obestatin (10, 30, and 100 mg/kg, intraperitoneally). One hour after indomethacin injection, gastric mucosal blood flow measurements were made by laser Doppler under urethane (1g/kg, i.p) anesthesia. Three hours later, the rats were decapitated and gastric lesions were scored. Stomach samples were obtained for the measurement of malondialdeyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and for histological examination. Values were compared by ANOVA.

    Results:
    Indomethacin resulted in severe damage of surface mucous cells and gastric pits as observed by light and scanning-electron microscopy. Lesion index, MDA level and MPO activity were increased with the induction of ulcer (p<0.01-0.001), while obestatin significantly decreased the gastric ulcer area in a dose-dependent manner and reduced myeloperoxidase activity and lipid peroxidation in the gastric tissue (p<0.05), but gastric GSH content was not changed by obestatin treatment. Neither of the obestatin doses significantly changed gastric mucosal blood flow.

    Conclusions:
    Obestatin alleviates indomethacin-induced gastric mucosal injury by a mechanism that is not associated with mucosal blood flow, but acts via the inhibition of neutrophil recruitment.

    To cite this abstract, please use the following information:
    Acta Physiologica 2011; Volume 203, Supplement 686 :PC263
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    i liked the first two posts! can you sum up the rest
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    I totally read all of that........
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