Effects Of Obestatin Research Articles

Unlocking the Potential of Obestatin: A Novel Peptide Intervention for Skeletal Muscle Regeneration and Prevention of Atrophy.

Obestatin is derived from the same gene as that of ghrelin and their functions were perceived to be antagonistic. Recent developments have shown that although they are known to have contradictory functions, effect of obestatin on skeletal muscle regeneration is similar to that of ghrelin. Obestatin works through a receptor called GPR39, a ghrelin and motilin family receptor and transduces signals in skeletal muscle similar to that of ghrelin. Not only there is a similarity in the receptor family, but also obestatin targets similar proteins and transcription factors as that of ghrelin (for example, FoxO family members) for salvaging skeletal muscle atrophy. Moreover, like ghrelin, obestatin also works by inducing the transcription of Pax7 which is required for muscle stem cell mobilisation. Hence, there are quite some evidences which points to the fact that obestatin can be purposed as a peptide intervention to prevent skeletal muscle wasting and induce myogenesis. This review elaborates these aspects of obestatin which can be further exploited and addressed to bring obestatin as a clinical intervention towards preventing skeletal muscle atrophy and sarcopenia.

Anti-inflammatory, anti-apoptotic, and antioxidant effects of obestatin on the colonic mucosa following acetic acid-induced colitis.

Cellular inflammatory processes, fibrogenesis, and apoptosis are the most characteristic pathologic features of colonic injury and colitis in human and experimental animals. Obestatin, a peptide derived from proghrelin, is reported to have significant protective and curative actions on many gastrointestinal tract inflammatory diseases, including ulcerative colitis. However, its exact protective mechanisms and the associated histopathological changes, are still in need of deeper exploration. This study explores the effect of obestatin on the course of acetic acid (AA)-induced colitis as an antifibrotic, anti-inflammatory, and anti-apoptotic agent in relation to associated tissue stress parameters. A total of 40 healthy male albino Wistar rats weighing 200-250 g were recruited in this study. The rats were classified into four groups (10 rats each); group I: control, group II: obestatin only treated (16 nmol/kg), group III: colitis induced group (AA 1 mL of 3.5% (v/v), and group IV: AA-induced colitis + obestatin for 14 days. Colonic samples were examined after staining haematoxylin and eosin, Alcian blue, Masson trichrome. The expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NFkB), and caspase-3 was estimated after immunohistochemical staining. Oxidative stress parameters, antioxidant enzymes, tissue myeloperoxidase (MPO) activity, ghrelin, and fibrogenesis markers were identified by immunoassay and colorimetric techniques. Colonic mucosa of group IV exhibited mucosal healing and regeneration of the surface epithelium with the restoration of the goblet cells' function together with a decline in PCNA, NFkB, and caspase-3 immunoreactivity in comparison to group III. This was accompanied by a reduction of the expression of fibrosis markers, hydroxyproline and fibronectin. In addition, tissue antioxidant status was significantly improved with a marked reduction of tissue MPO. Ghrelin level was significantly increased in comparison to group III. Group IV exhibited significant reduction in the levels of oxidative stress markers, malondialdehyde, total oxidant status with a marked increase in the activity of antioxidant enzymes, superoxide dismutase, catalase, and total cellular total antioxidant capacity. The concomitant treatment of obestatin inhibits the development of AA-induced colitis. The data signify that it has both curative and protective effects via antifibrotic, antioxidant, and anti-inflammatory activities.

Effect of obestatin on pituitary gonadal axis, leptin and MDA levels in type 2 diabetic Sprague Dawley Rats

Objective: To demonstrate the effect of Obestatin supplementation on oxidative stress and serum levels of testosterone, follicular stimulating hormone, luteinizing hormone and leptin in type 2 diabetic rats.
 Study Design: Laboratory-based experimental study
 Place and Duration of Study: Physiology Department, Army Medical College Rawalpindi from Mar-June 2015.
 Methodology: Forty-five healthy male Sprague Dawley rats were randomly divided into three groups. Group-I (healthy rats) were fed with regular pellet diet (NPD). Group-II (diabetic rats) and group-III (Obestatin treated diabetic rats) were fed with high-fat diet (HFD) followed by a single IP injection of Streptozotocin in the dose of 35 mg/kg on 15th day. After ten weeks, group-III was treated with intraperitoneal Obestatin (1 nmol/100ml). Blood samples were obtained by terminal intra-cardiac sampling for bioassays of Insulin, testosterone, FSH, LH, MDA and leptin by ELISA.
 Results: Obestatin supplementation in diabetic rats resulted in significant increase in FSH (9.4 ± 0.74 ng/dL), LH (3.89 ± 0.10 ng/dL) and testosterone levels (2.01 ± 0.09 ng/dL) in comparison with non-treated diabetic rats (7.04 ± 0.50 ng/dL), (1.70 ± 0.28 ng/dL) and (1.10 ± 0.40 ng/dL) respectively. Whereas leptin (3.91 ± 0.24 ng/dL) and MDA levels (1.75 ± 0.22 ng/dL) were reduced significantly when compared to the healthy rats (6.10 ± 1.29 ng/dL) and (1.96 ± 0.07 ng/dL) respectively.
 Conclusion: Testosterone levels are increased by Obestatin supplementation in type 2 diabetic rats by stimulating the pituitary-gonadal axis due to a decrease in circulating leptin levels and oxidative stress.

Involvement of obestatin, cyclin-dependent kinase and protein kinase C in control of feline ovarian cell viability and hormones release

The aim of our in vitro study was to understand the role of obestatin, cyclin-dependent kinase (CDK) and protein kinase C (PKC) in the control of basic feline ovarian cell functions (viability, ovarian hormones release), as well as the role of protein kinases in mediating the effect of obestatin on these processes. For this purpose, we analyzed the effect of obestatin (0, 10 and 100 ng/mL) alone or in combination with CDK blocker olomoucine (100 ng/mL) or PKC blocker calphostin-c (100 ng/mL) on cultured feline ovarian fragments or granulosa cells. The release of progesterone (P4), testosterone (T) and estradiol (E2) by isolated ovarian follicular fragments were evaluated by ELISA. Granulosa cell viability was analysed using the Trypan blue exclusion test. It was observed that the addition of obestatin alone significantly increased the granulosa cell viability (at dose 100 ng/mL), promoted the release of P4 (at all doses added) and IGF-I (at dose 100 ng/mL) but decreased T (at all doses added). E2 output was below the detection limit in all groups. The addition of either olomoucine or calphostin-c reduced cell viability, P4, T and IGF-I release. Both olomoucine and caplhostin-c inverted the stimulatory effect of obestatin on granulosa cell viability and were able to prevent stimulatory action of obestatin on ovarian cell viability and on hormone and growth factor release and change it to an inhibitory action. These observations show that obestatin can directly regulate (mostly promote) basal feline ovarian cell functions (hormone release and viability). The inhibitory action of CDK and PKC blockers on these functions suggests, that both CDK and PKC can be promoters of ovarian cell viability and steroidogenesis in cats. Furthermore, the ability of both CDK and PKC to prevent olomoucine action demonstrates that obestatin action on the feline ovary could be mediated by these kinases.

Protective Effect of Obestatin on Testicular Ischemia/Reperfusion Injury in Rats

Abstract Background: Testicular torsion (the most common cause of testicular ischemia) is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Al-though reperfusion of the testis is the key treatment after ischemia, it enhanced the formation of reactive oxygen species (ROS) that result in testicular damage and cell apoptosis. The effect of obestatin on testicular ischemia-reperfusion injury has not been evaluated previously. Aim of Study: This study was delineated to investigate the potential protective effect of obestatin on testicular ischemia/reperfusion (I/R) injury in rats. Material and Methods: 30 healthy adult male albino rats weighting 194-217g were involved and divided into 3 equal groups, group (I): Sham operated control group, group (II): Testicular ischemia reperfusion (I/R) group and group (III): Obestatin treated ischemia reperfusion (I/R-obestatin) group; received obestatin (100mg/kg) intravenously 15min before the testicular detorsion (reperfusion). Serum testosterone level was measured and orchiectomy was performed 6 hours after testicular detorsion and examined histopathologically and immunohistochemically for evaluation of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression. Testicular malondialdehyde (MDA), interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), caspase-8 and caspase-3 activities were also evaluated. Results: This study demonstrated that administration of obestatin prior to detorsion significantly increased the reduced serum testosterone level and attenuated the testicular tissue damage observed in I/R group. It also reversed the increased MDA, TNF-a and IL-1b levels and significantly enhanced the antioxidant enzymes activities in the ipsilateral I/R testis. Moreover, it improved the significant high levels of caspase-8 and caspase-3 and alleviated the increased Bax and the reduced Bcl-2 proteins expressions noticed in I/R testis. Conclusion: Obestatin has a protective effect against testicular I/R injury which can be attributed to its anti-oxidant, anti-inflammatory and anti-apoptotic properties.

Effects of ARC-hippocampus obestatin neural pathway on gastric motility and gastric emptying in diabetic rats

Objective: To investigate the obestatin neural projections from arcuate nucleus (ARC) to hippocampus in diabetic rats, and its effects on gastric motility and gastric emptying of rats. Methods: Diabetic model was established by fructose intake combined with streptozotocin injected intraperitoneally in healthy male Wistar rats. Diabetic rats were randomly divided into five groups: control group (NS group), 0.1, 1 and 10 pmol obestatin group, and obestatin + NBI27914 group, with 7 rats in each group. 0.5 μl saline (NS), obestatin (0.1 pmol, 1 pmol, 10 pmol) or the mixture (10 pmol obestatin + 60 pmol NBI27914) was injected into the hippocampus respectively, the gastric motility was recorded immediately after administration, and the gastric emptying was studied 15 min later. ARC-hippocampus obestatin neural pathway and ARC obestatin mRNA expression were compared between normal and diabetic rats with fluorogold (FG) retrograde tracing and immunofluorescence histochemical staining. Results: Compared with normal rats, the number of ARC FG/obestatin double labeled neurons and the expression level of ARC obestatin mRNA were decreased significantly in diabetic rats (P＜0.05); Obestatin could inhibit gastric motility and gastric emptying in a dose-dependent manner (P＜0.05~0.01) and the effects of obestatin could be partially blocked by NBI27914, an antagonist of corticotropin releasing factor receptor 1 (CRFR1) (P＜0.05). Compared with normal rats, the inhibitory effects of obestatin on gastric motility and gastric emptying were significantly decreased in diabetic rats (P＜0.05). Conclusion: There is an obestatin neural pathway between ARC and hippocampus, which participates in the regulation of gastric motility and gastric emptying in diabetic rats, and CRFR1 signal pathway is involved in this process. The damage of this neural pathway may participate in gastric motility dysfunction in early stage of diabetes.

Effect of obestatin on the migration and invasion of pancreatic tumor cells.

Effect of obestatin on the migration and invasion of pancreatic tumor cells.

The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism.

In order to investigate the role of the vagus nerve in the possible gastroprotective effect of obestatin on the indomethacin-induced acute oxidative gastric injury, Sprague-Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg, 5% NaHCO3) followed by obestatin (10, 30 or 100 μg/kg). In other sets of rats, surgical vagotomy (Vx) or selective degeneration of vagal afferent fibers by perivagal capsaicin was performed before the injections of indomethacin or indomethacin + obestatin (30 μg/kg). Gastric serosal blood flow was measured, and 4 h after ulcer induction gastric tissue samples were taken for histological and biochemical assays. Obestatin reduced the severity of indomethacin-induced acute ulcer via the reversal of reactive hyperemia, by inhibiting ulcer-induced neutrophil infiltration and lipid peroxidation along with the replenishment of glutathione (GSH) stores, whereas Vx abolished the inhibitory effect of obestatin on blood flow and lipid peroxidation, and worsened the severity of ulcer. On the other hand, serosal blood flow was even amplified by the selective denervation of the capsaicin-sensitive vagal afferent fibers, but obestatin-induced reduction in ulcer severity was not altered. In conclusion, the gastroprotective effect of obestatin on indomethacin-induced ulcer appears to involve the activation of the vagovagal pathway.

Effect of Obestatin on Hepatic Injury Induced by Renal Ischemia/Reperfusion in Rat

Background and Aims: Oxygen free radicals and cytokines are considered to be important components involved in the pathophysiological tissue alterations observed during Ischemia/Reperfusion (I/R). Based on the anti-oxidant and antiinflammatory effects of Obestatin (OB), we investigated the putative protective role of OB against I/R-induced oxidative remote organ injury. Materials and Methods: Male albino rats were subjected to either sham operation or bilateral renal artery clamping for 45 min and reperfusion for 24 h to induce I/R damage. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg. At the end of the experimental procedure, the rats were decapitated and hepatic tissue were removed for biochemical analyses of: Malondialdehyde (MDA), an end product of lipid peroxidation; the activity of antioxidant enzymes Superoxide Dismutase (SOD) and Catalase (CAT); the Myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration and the level of pro-inflammatory cytokines (TNF-α and IL-1β). The serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Lactate Dehydrogenase (LDH) levels were measured to assess liver function and tissue damage, respectively. Pathological histology was also performed. Results: The results revealed the occurrence of I/R- induced oxidative organ damage, as confirmed histologically and evidenced by an increase in the MDA level and MPO activity, and a decrease in activity of SOD and CAT. Furthermore, serum AST, ALT, LDH levels, and tissue cytokines were elevated in the renal I/R group as compared to the sham operated control group. On the other hand, obestatin treatment succeeded to modulate these observed abnormalities resulting from I/R as indicated by the reduction of MAD and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusion: Since obestatin administration reversed these oxidant responses, it seems likely that obestatin has a protective effect against oxidative organ damage induced by I/R.

Effect of Obestatin and its Fragment Analog Nt8U on the Epididymal and Brain Tissue of DIO‐C57BL/6 Mice

Imbalance in energy intake and energy expenditure due to change in lifestyles and genetic issues results in obesity which is a serious health problem. The entero‐endocrine system plays a major role in nutrient signaling. Appetite inducing signals and satiety peptides in the entero‐endocrine system have a definite role in management of obesity. Obestatin, a relatively new gastro‐peptide produced post translationally from preproghrelin gene and its N‐terminal fragment analog Nt8U (13 amino acids) have been shown to reduce food intake, gain in body weight, fat pads and also circulating lipids in normal adult male mice. In the present study, it is aimed to study the effect of these peptides on the epididymal and brain tissue of diet induced obese (DIO) mice. In an attempt to decipher their mechanism of action, it is intended to explore the changes these peptides bring about in the mouse brain at the genomic level. Mice fed with 60% (calorie by fat) high fat diet for a period of 19 weeks were administered obestatin and Nt8U intraperitoneally for 8 days and the mice maintained on HFD for 3 more weeks. Food intake and gain in bodyweight were monitored daily. Blood lipid parameters, plasma proteins and serum leptin levels were estimated after the administration regimen. No reduction in food intake or significant reduction in weight gain upon administration of the peptides. The leptin levels were drastically reduced from 21.7ng/dL in the saline treated mice to 10.4 and 8.9ng/dL in obestatin and Nt8U treated mice respectively. Triglyceride, cholesterol and HDL‐C levels were not altered after 8 days injection period but there was decrease in triglyceride levels by 30% in the Nt8U administered group and by 11% in the obestatin administered group 3 weeks after the treatment. Obestatin and Nt8U reduced epididymal fat by 7.5%. Estimation of serum enzymes SGPT, SGOT, ALP and LDH, weight and appearance of the organs showed the vital organs were unaffected by the treatment. mRNA from epididymal and brain tissue were extracted and subjected to Next Generation Sequencing (NGS). Analysis of NGS data revealed that, the genes Olr1, Alox 15, Gykl1 were upregulated in epididymal tissue and Cbr2, Btk in brain tissue. And, the genes Casq 1, Slc6a2, AldoB and Omp were down regulated in brain tissue. These differentially regulated genes modulate enzymes mainly involved in lipolysis and sequestration of triglycerides in the adipose tissue. In conclusion, administration of obestatin and Nt8U has a definite fat lowering effect as seen from reduced leptin levels. Reduction in triglycerides and the set of genes being differentially regulated strongly imply that there is alteration in lipid metabolism.Support or Funding InformationThis research is funded by Council of Scientific and Industrial Research (CSIR) India, Department of Biotechnology (DBT), India. The presenting author is grateful to Indian Council of Medical Research (ICMR), India for providing Senior Research Fellowship.

Obestatin and Its Fragments: A New Approach to the Regulation of Body Weight under Normal and Pathological Conditions

Gastrointestinal diseases and eating disorders are among the most common pathologies in the world. One of the most widespread and dangerous consequence of many eating disorders is an uncontrolled weight gain that often leads to obesity. This review focuses on the 15-year-long studies of obestatin, one of the potential regulators of eating behavior. This peptide contains 23 amino-acids and appears due to the processing of the preproghrelin gene responsible for the coding of another orexigenic protein ghrelin. Obestatin and ghrelin have multiple physiological functions, including appetite regulation. Obestatin was originally obtained from the gastric mucosa in rats, but subsequent studies showed that it could be expressed in various tissues and had different effects in various organs and tissues. This review emphasizes possible anorexigenic effects of this peptide and their mechanisms. Despite the 15 years of research on obestatin, its influence on different organs and the mechanism of anorexigenic effects in particular bring about a lot of discussion. This is primarily due to the ambiguity of the peptide receptors’ determination and is also related to the possible degradation of the molecule into small fragments, which, in turn, can have their own effects. The local effects of obestatin and its derivatives in peripheral tissues and the possible effect at the central level indicate the potential of these peptides for further studies. For example, these compounds can be considered as the potential therapeutic compounds for eating disorders’ treatment. The aim of this work was to describe the relevance of the problem associated with obesity treatment and to summarize the results of numerous studies on obestatin and its fragments and their effects on appetite regulation in order to explain its possible mechanisms.

Influence of obestatin on the histological development of the small intestine in piglets during the first week of postnatal life

Obestatin is a gastrointestinal peptide having wide-ranging effects on cell proliferation; however, its mechanism of action remains poorly understood. Thus, the aim of the study was to elucidate the effect of exogenous obestatin on the postnatal structural development of the small intestine. Seven-day-old piglets with an average BW of 1.56 ± 0.23 kg were divided into four groups (n = 10) that received intragastrically obestatin (2, 10 or 15 μg/kg BW) or vehicle. After a 6-day experimental period, morphological analysis of gastrointestinal tract and small intestine wall (mitosis and apoptosis indexes, histomorphometry of mucosa and muscularis layers) was performed. The study revealed a seemingly incoherent pattern of the histological structure of the small intestine among the experimental groups, suggesting that the effect of obestatin is both intestinal segment specific and dose dependent. Histomorphometric analysis of the small intestine showed that higher doses of obestatin seem to promote the structural development of the duodenum while simultaneously hindering the maturation of more distal parts of the intestine. Intragastric administration of obestatin increased the crypt mitotic index in all segments of the small intestine with the strongest pro-mitotic activity following the administration of obestatin at a dose of 10 and 15 μg/kg BW. The significant differences in the number of apoptotic cells in the intestinal villi among the groups were observed only in proximal jejunum and ileum. In conclusion, it seems that obestatin shows a broad-spectrum of activity in the gastrointestinal tract of newborn piglets, being able to accelerate its structural development. However, the varied effect depending on the intestinal segment or the concentration of exogenous obestatin causes that further research is needed to clarify the exact mechanism of this phenomenon.

A Comparative Study on the Protective Role of Obestatin, Quercetin and their Combination on the Injured Rat Gastric Mucosa Induced by Stress

AbstractBackground: Modern life contains a lot of nervous stresses which considered as the origin of many diseases.Aim of Study: Comparison between the protective effect of obestatin, quercetin and their combination on the stress-induced gastric ulcer in rats.Material and Methods: Sixty healthy adult Wistar male albino rats weighed 180-220g were used. Ten rats were con-sidered as normal control (Group I). Stress-induced gastric ulcers were produced in the other 50 rats. These rats were divided into 5 groups: Group II (with no medication), Group III (pretreated with misoprostol), Group IV (pretreated with obestatin), Group V (pretreated with quercetin) and Group VI (pretreated with both obestatin and quercetin). All medi-cations were used for 2 weeks before induction of ulcer.Results: In all groups the following parameters were measured; TBARS, antioxidant enzymes activities, myeloper-oxidase activity in gastric tissue, ulcer index, and plasma tumor necrosis factor-a. Comparing the results of Groups IV and V to that of Group II showed that, the use of obestatin or quercetin separately can ameliorate the condition to some extent with variable superiority. Also, the combined pretreat-ment of these rats with obestatin and quercetin produced more significant improvement; approaching normal; of all the tested parameters than the use of each drug separately. Moreover, the results in Group VI were far superior over the use of the standard drug misoprostol in Group III.Conclusion: The combined use of obestatin and quercetin as a prophylactic measure against the development of stress-induced gastric ulcer is more effective than the use of each drug separately.

Effect of Obestatin on Bone Turnover in Normal and Obese Male Albino Rats

Effect of Obestatin on Bone Turnover in Normal and Obese Male Albino Rats

Obestatin improve spatial memory impairment in a rat model of fetal alcohol spectrum disorders via inhibiting apoptosis and neuroinflammation

Clinical and experimental evidence have demonstrated that, use of alcohol during pregnancy can interrupt brain development. Alcohol-induced neurocognitive deficits in offspring's are involved with activation of oxidative-inflammatory cascade joined with extensive apoptotic neurodegeneration in different brain regions such as hippocampus. Obestatin is a newly discovered peptide with anti-inflammatory, antioxidant, activities in different animal models. In this study, we aimed to evaluate the protective effects of obestatin on alcohol-induced neuronal apoptosis and neuroinflammation in rat pups with postnatal ethanol exposure.Through intragastric intubation, ethanol (5/27 g/kg/day) was administered in male Wistar rat pups on postnatal days 2–10 (third trimester in humans). The animals received Obestatin (1 and 5 μg/kg, S.C.) on postnatal days 2–10. Thirty-six days after birth, the spatial memory test was performed using Morris water maze test, and then, antioxidant enzymes and TNF-α levels were measured by ELISA assay. The expression level of GFAP and caspase-3 proteins was determined via immunohistochemical staining after the behavioral test.Obestatin significantly improved spatial memory deficits (P < .01), and obestatin treatment could significantly increase glutathione and total superoxide dismutase activity (P < .05), reduce level of malondialdehyde (P < .05) and TNF-α in comparison with the ethanol group (P < .01). It's also reduced caspase-3 level, and decreased GFAP-positive cells in the hippocampus of ethanol-exposed rat pups (P < .01). The result of this study shows the potential involvement of oxidative-inflammatory cascade-mediated apoptotic signaling in cognitive deficits due to postnatal ethanol exposure, the results also indicated the neuroprotective effects of Obestatin on alcohol-related behavioral, biochemical and molecular deficits.

Effect of Obestatin on Gastric Acid Secretion and Mucin Expression in Normal and Streptozoocin Induced Diabetic Rats

Effect of Obestatin on Gastric Acid Secretion and Mucin Expression in Normal and Streptozoocin Induced Diabetic Rats

Molecular studies on preproghrelin gene: alternative splicing, obestatin effects, coding region and variants

Molecular studies on preproghrelin gene: alternative splicing, obestatin effects, coding region and variants

Obestatin may affect the GnRH/KNDy gene network in sheep hypothalamus

The effects of obestatin on gonadotrophic axis activity in ruminants have not yet been determined. The aim of this study was to investigate the effect of intracerebroventricular infusions of obestatin on the gonadotrophin-releasing hormone (GnRH) mRNA and protein expressions as well as on KNDy mRNA and kisspeptin (Kiss) peptide expressions in peripubertal female sheep. Animals were randomly divided into two groups: the control group received intracerebroventricular infusions of the vehicle, and the obestatin group was infused with obestatin (25 μg/120 μL h−1). The series of four 1-h infusions per day during three consecutive days were performed. After the end of the experiment parts of sheep brains were fixed in situ for immunohistochemical analysis, while the remaining brains were frozen for Real Time qPCR analysis.Substantial changes in the activity of the GnRH and KNDy gene network were observed in obestatin-infused sheep. In those animals an increase of GnRH mRNA expression in the preoptic area, a decrease of GnRH mRNA expression in the median eminence and an increase of GnRH immunoreactivity in the median eminence were found. Moreover, changes in the KNDy mRNA expression in mediobasal hypothalamus as well as decrease Kiss expression in arcuate nucleus and median eminence were observed.It was revealed that obestatin affects the GnRH and KNDy gene network as well as Kiss at the level of mRNA and protein expression. Thereby, it can be concluded that obestatin participates in the mechanism modulating gonadotrophic axis activity at the central level in peripubertal female sheep.

Short-term effects of obestatin on hexose uptake and triacylglycerol breakdown in human subcutaneous adipocytes.

AIMTo study complete dose-dependent effects of obestatin on lipolytic and glucose transport activities in human adipocyte preparations highly responsive to insulin.METHODSAdipocytes were prepared by liberase digestion from subcutaneous abdominal adipose tissue obtained from overweight subjects undergoing plastic surgery. The index of lipolytic activity was the glycerol released in the incubation medium, while glucose transport was assessed by [3H]-2-deoxyglucose uptake assay.RESULTSWhen tested from 0.1 nmol/L to 1 μmol/L, obestatin did not stimulate glycerol release; it did not inhibit the lipolytic effect of isoprenaline and did not alter the insulin antilipolytic effect. Obestatin hardly activated glucose transport at 1 μmol/L only. Moreover, the obestatin stimulation effect was clearly lower than the threefold increase induced by insulin 100 nmol/L.CONCLUSIONLow doses of obestatin cannot directly influence lipolysis and glucose uptake in human fat cells.

Protective effect of obestatin on indomethacin-induced acute gastric ulcer in rats: role of VEGF and TNF-α

Background Gastric ulcer (GU) is one of the most common disorders that affect the gastrointestinal tract. Obestatin, a ghrelin-related peptide, has been shown to exhibit some protective and therapeutic effects in the gut. Aim This study aimed at investigating the protective effect of obestatin on acute indomethacin (IND)-induced GU, clarifying the role of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α). Materials and methods A total of 32 adult Wistar albino male rats were divided into four main groups: control group, obestatin group, GU group, and obestatin+GU group. Obestatin was given by a single intraperotineal injection (30 µg/kg) 1 h before induction of GU by a single oral dose of IND (40 mg/kg). Pyloric ligation was carried out in all animals before IND or distilled water administration. Four hours later after IND treatment, gastric ulcer index, preventive index, gastric juice volume, and free and total acidity were assessed. Nitric oxide, VEGF mRNA, and TNF-α mRNA were measured in gastric tissue, as well as histopathological study of gastric injury. Results IND caused a significant increase in ulcer index, gastric juice volume, free and total acidity, and TNF-α mRNA, with a significant decrease in nitric oxide and VEGF mRNA. Pretreatment with obestatin reversed these effects. Conclusion Obestatin pretreatment showed a gastroprotective effect against the IND-induced GU that can be explained by the anti-inflammatory and angiogenic effects of obestatin treatment and reduction of gastric juice volume, free acidity, and total acidity.