Development of alginate/chitosan hydrogel loaded with obestatin and evaluation of collagen type I, III, VEGF and TGF-ß1 gene expression for skin repair in a rat model (in vitro and in vitro study).

BACKGROUND: Skin injuries have long been recognized as a prevalent type of physical injury. As a result, numerous research studies have been performed to discover an effective mechanism for wound healing. Therefore, tissue engineering of skin has developed as a potential solution for traditional methods of treating skin injuries. METHODS AND MATERIALS: Alginate/Chitosan hydrogel was mixed with 1, 10, 100, and 150 µM Obestatin, and evaluated the morphology, cumulative release, hemocompatibility and cytocompatibility, water absorption, cell viability, weight loss, and antibacterial characteristics of three-dimensional (3D) alginate (Alg) and chitosan (Cs) hydrogels during the process of wound curing. Various concentrations of Obestatin (Obes) were utilized for this purpose. Finally, the hydrogels that were made were tested on a full-thickness dermal wound in a Wistar rat model. The curative effects were determined by analyzing RNA expression and examining tissue stained with Masson's trichrome (MT) and hematoxylin-eosin (H&E). RESULTS: The biodegradability of this hydrogel was verified using weight loss testing, which demonstrated a reduction of around 90% after a period of 3 days. Furthermore, the MTT assay demonstrated that hydrogels have a beneficial effect on cell proliferation without inducing any harmful effects. Furthermore, the hydrogels produced demonstrated higher wound closure in vivo compared to the wounds treated with gauze (negative control group). Among the hydrogel groups, the chitosan/alginate/obestatin 100 µM group exhibited the apical percentage of wound closure, gene expression, and secondary epithelialization, but in 150 µM concentrations, we saw a lower rate of cell growth and proliferation and increase in hemolysis. In addition, RT-PCR analysis demonstrated that a concentration of 100 µM obestatin resulted in an upregulation in the expression of mRNA for vascular endothelial growth factor (VEGF), collagen type I & type III, and transforming growth factor-beta (TGF-ß). CONCLUSION: The present study suggests that 3D Alg/Cs hydrogels with a concentration of 100 µM obestatin have the potential for clinical application in the treatment of skin injuries.

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.

Unveiling the Ghrelin and Obestatin Roles in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis Assessing Their Pathogenic Implications and Biomarker Utility.

BACKGROUND: Inflammatory bowel disease (IBD), pathologically known as chronic inflammation of the gastrointestinal tract, is among the diseases with a high burden worldwide. Ghrelin and obestatin, as adipocytokines mainly in adipose tissues, are involved in immune responses and inflammatory pathways. Studies have assessed the circulatory ghrelin levels in patients with IBD. Herein, we aim to pool these studies through systematic review and meta-analysis. METHODS: Four international databases, PubMed, Embase, Scopus, and the Web of Science were systematically searched for studies assessing ghrelin or obestatin levels in patients with IBD (either Crohn's disease [CD] or ulcerative colitis [UC]) in active phase or in remission. Random-effects meta-analysis was conducted in order to calculate the pooled estimate using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Nineteen studies were included in our systematic review, comprising 1064 patients with IBD (476 UC and 588 CD). A meta-analysis of 11 studies for comparison of active and quiescent disease showed that patients with active IBD had significantly higher levels of ghrelin (SMD, 0.70; 95% CI, 0.06 to 1.34; P = .03). However, in separate analyses for UC or CD, no such difference was observed (SMD, 1.30; 95% CI, -0.28 to 2.88, P = .11; and SMD, 0.80; 95% CI, -0.41 to 2.01; P = .20, respectively). No significant difference was also observed in ghrelin levels between patients with active IBD and healthy control subjects. Obestatin levels also were not different between patients with active disease and those in remission (SMD, 0.31; 95% CI, -0.05 to 0.68; P = .09). On the other hand, the obestatin/ghrelin ratio was significantly lower in patients with active IBD (SMD, -1.90; 95% CI, -2.45 to -1.35; P < .01). CONCLUSIONS: Our results demonstrate that IBD patients with active disease have higher levels of ghrelin, which needs to be confirmed in future studies. Also, the obestatin/ghrelin ratio might be a promising biomarker for the assessment of disease activity.

Ghrelin, as an adipokine, can be a potential biomarker for distinguishing active inflammatory bowel disease from disease remission. Obestatin/ghrelin ratio was also significantly lower in patients with active inflammatory bowel disease. These biomarkers should be investigated in future studies.

Ghrelin and obestatin can promote human ovarian granulosa cell functions and FSH effects.

The aim of the present in-vitro experiments was to examine the direct influence of ghrelin and obestatin on viability, proliferation and progesterone release by human ovarian granulosa cells and their response to FSH administration. Human granulosa cells were cultured in presence of ghrelin or obestatin (both at 0, 1, 10 or 100 ng/ml) alone or in the presence of FSH (10 ng/ml). Cell viability, accumulation of proliferation markers PCNA and cyclin B1 and release of progesterone were analyzed by Trypan blue extrusion test, quantitative immunocytochemistry and ELISA. Ghrelin, obestatin and FSH up-regulated all the measured ovarian cell parameters. Moreover, both ghrelin and obestatin promoted all the stimulatory effects of FSH. The obtained results demonstrate the direct stimulatory action of ghrelin, obestatin and FSH on basic ovarian cell functions, as well as the ability of metabolic hormones to improve FSH action on human ovarian cells.

Cardio-Protective Role of a Gut Hormone Obestatin: A Narrative Review.

Obestatin is a gut hormone composed of 23 amino acids that play a role in protecting the heart. It is synthesized from the same preproghrelin gut hormone gene as another gut hormone. The function and receptor of obestatin remain controversial, despite being present in various organs such as the liver, heart, mammary gland, pancreas, and more. The activity of obestatin is opposite to that of ghrelin, another hormone. The GPR-39 receptor is used by obestatin to exert its effects. Obestatin's cardioprotective role can be attributed to its ability to affect various factors, including adipose tissue, blood pressure regulation, heart, ischemia-reperfusion injury, endothelial cells, and diabetes. Because these factors are related to the cardiovascular system, modifying them via obestatin can provide cardioprotection. Furthermore, ghrelin, its antagonist hormone, regulates cardiovascular health. Diabetes mellitus, hypertension, and ischemia-reperfusion injury can all alter ghrelin/obestatin levels. Obestatin has also been shown to impact other organs, reducing weight and appetite, inhibiting food intake, and increasing adipogenesis. Obestatin has a brief half-life and is quickly degraded by proteases in the blood, liver, and kidneys after entering circulation. This article offers insights into the cardiac function of obestatin.

Development of a sensitive and quantitative HPLC-FLD method for the determination of obestatin in human plasma.

Obestatin is a gastrointestinal system peptide. The quantification of this peptide is conventionally performed using immunological techniques. In this study, a selective and sensitive HPLC method coupled with fluorescence detection for the quantitation of obestatin in human plasma was developed and validated. The separation was obtained on a C18 (4.6 × 100 mm, 3.5-µm particles) column using a mobile phase composed of acetonitrile and water, both including 0.1% trifluoroacetic acid. The developed method was found to be linear in the concentration range of 20 to 1000 ng/mL, with a coefficient of determination of 0.9982. The precision results were less than 10%, and the accuracy results were between 92% and 107%. The detection and quantification limit values were obtained as 2.8 and 9.4 ng/mL, respectively. Analyte solutions were found stable for 24 h at room temperature, three freeze-thaw cycles, and 2 weeks at -20°C. The developed method was successfully used for the quantification of obestatin in human plasma samples. In conclusion, the developed method is sensitive and specific for measuring the plasma concentrations of obestatin.

ß-N-Methylamino-L-Alanine (BMAA) Modulates the Sympathetic Regulation and Homeostasis of Polyamines.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1-1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues-regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors.

Variations of Ghrelin and Obestatin Hormones During the Menstrual Cycle of Women of Different BMIs.

Introduction: The cyclical changes of hormones during the menstrual cycle are responsible not only for reproductive function but also have other effects on dietary intake and appetite. The current study aimed to investigate the variations of appetite-related hormones (ghrelin and obestatin) during the menstrual cycle and their association with adipokines, estrogen, and BMI. Methods: Fifty-six regularly menstruating female students were grouped into normal weight (BMI ≤24.9; n = 26), and overweight/obese subjects (BMI ≥25; n = 30). Serum ghrelin, obestatin, leptin, adiponectin, and estrogen levels were measured during the early follicular, preovulatory, and luteal phases of the menstrual cycle using the ELISA technique. Results: There were insignificant differences in the levels of serum ghrelin, obestatin, and ghrelin/obestatin ratio across menstrual cycle phases in the whole cohort as well as in each group separately (p > 0.05). Serum ghrelin was significantly less in OW-OB as compared to the NW group (p = 0.005), whereas the average serum obestatin did not show any significant differences between the two groups. No significant correlation was seen between ghrelin and obestatin with the adipokines and estradiol. Conclusion: Significant low level of ghrelin was observed in obese group during the follicular phase. This finding may provide new insights into the altered ghrelin patterns in OW-OB individuals, as a cause or a consequence of obesity and related menstrual disorders.

Narrative-focused Group Counseling Improves Intervention Outcomes in Women With Obesity.

OBJECTIVE: To investigate the effects of narrative group counseling combined with diet modification and exercise plans on weight loss in Iranian women with obesity. DESIGN: Parallel 2-arm clinical trial. PARTICIPANTS: Fifty-six Iranian women with obesity (aged 18-50 years). INTERVENTION: The intervention group included weekly diet, exercise, and narrative-focused group counseling, whereas the comparison group included dietary modification and exercise sessions for 8 months (32 sessions). MAIN OUTCOME MEASURE: Anthropometric and body composition parameters, blood biochemical parameters (high-density lipoproteins, low-density lipoproteins, triglycerides, fasting blood sugar, ghrelin, obestatin), physical activities, and appetite scores. ANALYSIS: McNemar test was used for the variables that were not normally distributed and for scaling. Furthermore, t tests were used to compare quantitative variables with normal distributions. The original P (0.05) was adjusted to P = 0.0031 using the Bonferroni correction. RESULTS: Weight, body mass index, body fat proportion, and hip circumference decreased significantly in the intervention vs comparison group. Serum low-density lipoproteins, triglycerides, total cholesterol, fasting blood sugar, appetite score, and ghrelin decreased, whereas obestatin increased significantly in the intervention vs comparison group. CONCLUSIONS AND IMPLICATIONS: Narrative-focused group counseling combined with traditional strategies was effective in achieving significant changes in weight, body mass index, and appetite. Future studies with a more diverse audience and a longer follow-up are warranted.

Diagnostic value of serum levels of galanin and obestatin in patients with gastric cancer

SUMMARY OBJECTIVE: Gastric cancer ranks the third among the cancer-related deaths. It is diagnosed at advanced stage in many patients due to malignant proliferation and has a poor prognosis. Currently, no instrument or biomarker has been proven to diagnose the disease before the advanced stages. This study aimed to measure the serum levels of galanin and obestatin, which were examined in various studies including cancer studies, and to discuss their diagnostic value in gastric cancers. METHODS: In this study, 30 adult patients with gastric cancer and 30 healthy adults in the control group were examined prospectively. The demographic characteristics and serum levels of galanin and obestatin in the patient and control groups were recorded. RESULTS: The mean serum level of galanin in the patient and control groups was 19.73±5.04 and 35.59±10.94 pg/mL, respectively. The mean serum level of obestatin in the patient and control groups was 40.21±5.82 and 15.15±3.32 ng/mL, respectively. A significant difference was found between the groups (p<0.001). CONCLUSION: Serum levels of galanin were lower and serum levels of obestatin were higher in patients with gastric cancer compared to the healthy individuals. Serum levels of obestatin and galanin can be used as potential biomarkers in the diagnosis of gastric cancer.

[Metabolic profile and concentration of ghrelin and obestatin in children and adolescents with obesity]. / Perfil metabólico, concentración de grelina y obestatina en niños y adolescentes con obesidad.

Background: It has been pointed out that ghrelin and obestatin could have an impact on the genesis of obesity, since they estimulate and inhibit apetite and, therefore, food consumption. Objective: To compare the metabolic profile, lipid profile and the concentrations of ghrelin and obestatin in children with normal weight or obesity. Material and methods: Cross-sectional design with 97 normal weight or obese children, 6 to 18 years of age, who did not present systemic diseases. The serum concentrations of glucose, insulin, total cholesterol, triglycerides, high (HDL), low (LDL) and very low density (VLDL) lipoproteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), ghrelin and obestatin were determined. Descriptive statistics were performed. Student's t test was used to compare groups, and correlation coefficients of ghrelin and obestatin values with biochemical and anthropometric variables. A p value of ≤ 0.05 was significant. Results: 55 children with normal weight and 42 with obesity were included; mean age was 10.7 years. Triglycerides, LDL, VLDL, ALT and insulin were higher, and HDL lower in obese children (p < 0.05). Ghrelin values were higher in normal weight children (p < 0.05), and there was no difference in obestatin values. Conclusions: The lower concentration of ghrelin in obese children may indicate a negative feedback to regulate energy consumption. Children and adolescents with obesity show metabolic and lipid profile alterations that place them at risk of early development of cardiovascular risk factors.

Introducción: se ha señalado que la grelina y la obestatina podrían incidir en la génesis de la obesidad al estimular o inhibir el apetito y, por ende, el consumo de alimentos. Objetivo: comparar el perfil metabólico, el perfil de lípidos y las concentraciones de grelina y obestatina en niños con normopeso u obesidad. Material y métodos: diseño transversal con 97 niños de 6 a 18 años con normopeso u obesidad que no presentaran enfermedades sistémicas. Se determinaron las concentraciones séricas de glucosa, insulina, colesterol total, triglicéridos, lipoproteínas de colesterol de alta (HDL), baja (LDL) y muy baja densidad (VLDL), aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), grelina y obestatina. Se usó estadística descriptiva. Se utilizó la prueba t de Student para comparar grupos, y coeficientes de correlación de los valores de grelina y obestatina con las variables bioquímicas y antropométricas. Un valor de p ≤ 0.05 fue significativo. Resultados: se incluyeron 55 niños con normopeso y 42 con obesidad; la edad promedio fue de 10.7 años. Los triglicéridos, LDL, VLDL, ALT y la insulina fueron superiores, y el HDL inferior en niños con obesidad (p < 0.05). Los valores de la grelina fueron superiores en niños con normopeso (p < 0.05) y no hubo diferencia en los de la obestatina. Conclusiones: la menor concentración de grelina en niños con obesidad puede indicar una retroalimentación negativa para regular el consumo de energía. Los niños y adolescentes con obesidad muestran alteraciones metabólicas y del perfil de lípidos que los ponen en riesgo de desarrollar tempranamente factores de riesgo cardiovascular.

The association of a body shape index and visceral adiposity index with neurotrophic, hormonal and metabolic factors among apparently healthy women: a cross-sectional analysis.

Purpose: A body shape index (ABSI) and visceral; adiposity index (VAI) can reflect some cardio-metabolic risk factors in the population. To the best of our knowledge, there are no previous studies conducted on the assessment of the association between neurotrophic factors, Ghrelin and Obestatin with ABSI and VAI. We aimed to investigate this association among apparently healthy women. Methods: Ninety apparently healthy women were recruited in the present study. All participants were in need of dietary intervention for weight loss and participated in the study before receiving any intervention. Dietary, anthropometric, physical activity, stress level and biochemical assessments, as well as blood pressure measurements were done for all participants. Results: Women in the highest tertile of ABSI had significantly lower SBP compared to the lowest ABSI tertile. Women who were in the highest tertile of VAI had significantly lower serum Obestatin levels compared to the first and second tertiles in both crude and adjusted comparisons. Serum NGF, Obestatin and Ghrelin levels were significantly lower in the highest tertile of VAI compared to the lowest tertile in both crude and adjusted comparisons. HOMA-IR, serum insulin, LDL-C, TG and TC were significantly higher in the highest tertile of VAI compared to the lowest tertile. QUICKI in the highest tertiles were significantly lower than the first tertile in adjusted model. Conclusion: This evidence can be useful for researchers in applying appropriate anthropometric indices regarding different populations with multifactorial metabolic complications. The current findings need approving by prospective population study and also clinical trial researches.

Investigation of the association between cardio-metabolic risk factors, neurotrophins and gastric hormones among apparently healthy women: A cross-sectional analysis.

Introduction: Although, some evidence has shown that obestatin, ghrelin, and neurotrophic factors can be involved in the development of cardio-metabolic risk factors, there are some contradictions in this regard. We aimed to investigate the association of serum neurotrophic factors and some gastric hormones with cardio-metabolic risk factors among apparently healthy women. Methods: In the present study, 90 apparently healthy women were recruited by a convenient sampling method from the nutrition counseling clinic in Tabriz, Iran. All participants need dietary counseling for weight loss and were recruited before receiving any dietary interventions. Anthropometric, biochemical, physical activity, and blood pressure (BP) measurements, as well as dietary assessment, were done in all participants. Results: Women who were in the highest tertile of serum obestatin levels (OR=0.118, 95% CI:0.035-0.396) had a significantly lower risk for development of hypertriglyceridemia compared to the reference group (Ptrend < 0.001). Participants in the highest tertile of serum ghrelin had a significant lower risk of hypertriglyceridemia, hyperglycemia, low HDL-C, and MetS (Ptrend < 0.05). Women who were in the higher tertile of serum NGF levels had a significantly lower risk for development of hypertriglyceridemia after adjustment for potential confounding variables (OR=0.091, 95% CI: 0.023-0.361 and OR=0.193, 95% CI: 0.057-0.649 respectively). Conclusion: In the current study serum levels of obestatin, NGF, and ghrelin were associated with some cardio-metabolic risk factors such as hypertriglyceridemia and MetS. It seems that these factors are associated with metabolic regulation. However, further studies are needed to substantiate this claim.

Diverse and Complementary Effects of Ghrelin and Obestatin.

Ghrelin and obestatin are two "sibling proteins" encoded by the same preproghrelin gene but possess an array of diverse and complex functions. While there are ample literature documenting ghrelin's functions, the roles of obestatin are less clear and controversial. Ghrelin and obestatin have been perceived to be antagonistic initially; however, recent studies challenge this dogma. While they have opposing effects in some systems, they function synergistically in other systems, with many functions remaining debatable. In this review, we discuss their functional relationship under three "C" categories, namely complex, complementary, and contradictory. Their functions in food intake, weight regulation, hydration, gastrointestinal motility, inflammation, and insulin secretion are complex. Their functions in pancreatic beta cells, cardiovascular, muscle, neuroprotection, cancer, and digestive system are complementary. Their functions in white adipose tissue, thermogenesis, and sleep regulation are contradictory. Overall, this review accumulates the multifaceted functions of ghrelin and obestatin under both physiological and pathological conditions, with the intent of contributing to a better understanding of these two important gut hormones.

The Impact of Sleep-Disordered Breathing on Ghrelin, Obestatin, and Leptin Profiles in Patients with Obesity or Overweight.

BACKGROUND: The impact of concomitant obesity and sleep disorders on neuropeptides related to energy balance is poorly understood. The aim of this study was to assess the nocturnal profile of total ghrelin, obestatin, and leptin in patients with elevated BMI and to investigate the impact of breathing-related sleep disorders on these hormone levels. METHODS: The study involved 58 patients with suspicion of obstructive sleep apnea (OSA). Patients underwent anthropometric and sleep examination and measurements of night ghrelin, leptin, and obestatin levels. RESULTS: In patients with OSA (n = 46), recognized on the basis of sleep examination outcomes, the correlation of anthropometric measurements with parameters of sleep disorders and ghrelin levels was observed, contrary to the control group (n = 12). In the OSA group, levels of ghrelin were significantly lower than in the control group at 5:00 and 7:00. Levels of leptin in the OSA group were also lower than those in the control groups (not statistically significant). Profiles of obestatin in both groups were similar. CONCLUSIONS: Our results confirm the relationship between obesity and sleep-disordered breathing. Both these disorders affect ghrelin levels-parameters of obesity negatively correlate with hormone concentration, and OSA seems to lower ghrelin values in the second half of the night.

Acetate-mediated-obestatin modulation attenuates adipose-hepatic dysmetabolism in high fat diet-induced obese rat model.

PURPOSE: Approximately 650 million of world adult population is affected by obesity, which is characterized by adipose and hepatic metabolic dysfunction. Short chain fatty acids (SCFAs) have been linked to improved metabolic profile. However, the effect of SCFAs, particularly acetate on adipose-hepatic dysfunction is unclear. Therefore, the present study investigated the role of acetate on adipose-hepatic metabolic dysfunction and the possible involvement of obestatin in high fat diet-induced obese Wistar rats. METHODS: Adult male Wistar rats (160-190 g) were allotted into groups (n = 6/group): Control, acetate-treated, obese and obese + acetate-treated groups received vehicle (distilled water), sodium acetate (200 mg/kg), 40% HFD and 40% HFD plus sodium acetate respectively. The administration lasted for 12 weeks. RESULTS: HFD caused increased body weight gain and visceral adiposity, insulin resistance, hyperinsulinemia and increased pancreatic-ß cell function and plasma/hepatic triglyceride and total cholesterol as well as decreased adipose triglyceride and total cholesterol, increased plasma, adipose, and hepatic malondialdehyde, TNF-α, uric acid, lactate production and plasma/adipose but not gamma-glutamyl transferase and decreased plasma, adipose, and hepatic nitric oxide, glucose-6-phosphate dehydrogenase (G6PD), glutathione (GSH) and obestatin concentration compared to the control group. Notwithstanding, treatment with acetate attenuated the alterations. CONCLUSIONS: The results demonstrate that high fat diet-induced obesity is characterized with adipose and hepatic lipid dysmetabolism, which is associated with obestatin suppression. Findings also suggest that acetate provide protection against adipose and hepatic metabolic perturbations by restoring obestatin as well as G6PD/GSH-dependent antioxidant system.

Concurrent Akt, ERK1/2 and AMPK Activation by Obestatin Inhibits Apoptotic Signaling Cascades on Nutrient-Deprived PC12 Cells.

Targeting apoptosis in the ischemic penumbra is a rational therapeutic approach for restricting cerebral infarct volume after clinical stroke. The present work explored the capability of the obestatin peptide, as a novel approach to inhibit apoptotic signaling cascades on PC12 cells. According to the results, obestatin treatment significantly reduced nutrient deprivation-induced apoptotic cell death. The protective effects were related to the regulation of the anti-apoptotic protein, BCL-2, and the apoptotic protein caspase-3. This encompasses the control of apoptosis by the interplay between Akt, ERK1/2 and AMPK signaling pathways. The activation of Akt and AMPK was concomitant with the phosphorylation of their downstream targets, GSK3 and ACC, respectively. Besides, obestatin also causes FoxO1 nuclear export supporting the prevention of the apoptosome formation. The concurrent activation of Akt and AMPK by obestatin via the GPR39 receptor, supports a role for this system in the balance concerning the catabolic and the anabolic signaling to sustain cellular function and viability. Furthermore, these results provide both an insight into how the obestatin/GPR39 system regulates anti-apoptotic pathways, and a framework for ascertaining how this system can be optimally targeted in treatment of brain cell death after stroke.

FumDSB Can Reduce the Toxic Effects of Fumonisin B1 by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs.

Fumonisin B1 (FB1) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB1 ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1 group was supplemented with FB1 at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1 group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1 can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1 were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1 by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.

Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome.

OBJECTIVE: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. METHODS: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. RESULTS: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. CONCLUSION: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

Associations of Obstructive Sleep Apnea, Obestatin, Leptin, and Ghrelin with Gastroesophageal Reflux.

Gastroesophageal reflux disease (GERD) is commonly observed in patients with obstructive sleep apnea (OSA). Hormonal disorders observed in OSA may be relevant in the development of GERD. The aim of the study was to assess the correlations between ghrelin, obestatin, leptin, and the intensity of GERD in patients with OSA. The study included 58 patients hospitalized due to clinical suspicion of sleep disorders during sleep. All patients underwent a sleep study, and blood samples were collected overnight for hormonal tests. Survey data concerning symptoms of GERD, gastroscopy, and esophageal pH monitoring results were included in the study. In patients with OSA, GERD was twice as common when compared to the group without OSA. Among subjects with severe sleep apnea (AHI > 30; n = 31; 53%), we observed lower ghrelin levels, especially in the second half of the night and in the morning (p5.00 = 0.0207; p7.00 = 0.0344); the presence of OSA had no effect on obestatin and leptin levels. No significant differences in hormonal levels were observed between the groups depending on the diagnosis of GERD. However, correlations of ghrelin levels with the severity of esophagitis, leptin and ghrelin levels with the severity of GERD symptoms, and leptin levels with lower esophageal pH were found. GERD is more frequent among patients with OSA. In both GERD and OSA, deviations were observed in the levels of ghrelin and leptin. However, our analysis demonstrates that the relationship between OSA and GERD does not result from these disorders.