Ghrelin Content Research Articles

Gut–brain bidirectional determination in regulating the residual feed intake of small-sized meat ducks

The gut-brain axis is essential in maintaining the homeostasis of neuronal system, endocrine system, and intestinal microbiota in both the afferent and efferent directions. This axis is considered to be a key mechanism that regulates feed efficiency (FE). This study aimed to investigate the regulatory mechanisms of gut-brain axis-related genes on the residual feed intake (RFI) in H-strain small-sized meat ducks. A total of 500 ducks with similar initial BW (635.2 ± 15.1 g) were selected and reared in the same experimental facility until slaughter at 42 d of age. RFI was calculated from the average daily gain (ADG), average daily feed intake (ADFI), and metabolic body weight (MBW0.75). Thirty high-RFI (H-RFI) and 30 low-RFI (L-RFI) birds were selected for further evaluation of growth performance, carcass characteristics, and blood biochemical parameter measurements. Six L-RFI and 6 H-RFI birds were then subjected to hypothalamic transcriptomic and cecal microbial sequencing analyses. Results indicated that L-RFI birds exhibited lower production performance (ADFI, FCR, and RFI) and blood biochemical indices (total cholesterol and ghrelin content) compared with H-RFI birds (P < 0.05). Gene expression differed significantly between the L-RFI and H-RFI birds, with 70 upregulated and 50 downregulated genes. The bacterial communities of L-RFI birds showed higher abundances of Bacteroides, Bifidobacterium, and Lactococcus, and lower abundances of Erysipelatoclostridium, Parasutterella, Fournierella, and Blautia compared with H-RFI birds (P < 0.05). Interactive analysis revealed bacterial communities associated with FE were significantly correlated with hypothalamic genes (P < 0.05), for example, Bacteroides was positively correlated with DGKH and LIPT2, while negatively correlated with CAPN9, GABRD, and PDE1A. Bifidobacterium showed significant correlations with ATP2A3, CALHM6, and TMEM121B. Overall, RFI was a crucial indicator of FE, regulated by interactions between brain gene expression and gut microbiota through cAMP signaling, neuroactive ligand-receptor interaction, and calcium signaling pathways. Notably, increased expression of hypothalamic genes and abundance of carbohydrate-utilization microbiota in L-RFI meat ducks improved FE by enhancing energy metabolism and volatile fatty acids absorption.

Assessment of adenohypophysis function and ghrelin level in children with biologically inactive growth hormone syndrome

Background. Mutations in the growth hormone (GH) gene cause various forms of biologically inactive growth hormone (BIGH) syndrome. Ghrelin potentiates the secretion of GH. Ade­nohypophysis hormones take part in human growth mechanisms. Insulin-like growth factor 1 (IGF-1) level is a criterion of GH activity. The purpose of the study was to assess the adenohypo­physis functions and to determine the role of ghrelin in patients with BIGH syndrome to optimize the diagnosis and treatment. Materials and methods. Anthropometric parameters were evalua­ted in 158 children with BIGH syndrome whose average age was 7.83 ± 1.23 years. The function of the adenohypophysis was evalua­ted accor­ding to the levels of somatotropin, thyroid-sti­mulating, adrenocorticotropic, luteinizing, follicle-stimulating hormone and their corresponding peripheral hormones, which were determined by radioimmunological methods and chemiluminescent immunoassay. A statistical analysis of the results was carried out. Results. The release of GH against the background of clonidine and insulin tests in patients with BIGH syndrome was higher than 10 ng/ml, the basal level of IGF-1 was significantly lower than the reference values. After a 4-day test for sensitivity to GH, the level of IGF-1 increased more than 2 times. Against the background of treatment with recombinant GH, serum thyroid-stimulating, adrenocorticotropic hormone, and cortisol indicators changed significantly, but their levels fluctuated within the reference values. Significant changes in ghrelin content were detected 120 minutes after falling asleep. Most children with BIGH syndrome had timely sexual development, precocious puberty was revealed in 19 children, the smallest was the group with delayed puberty (5 children). Gonadotropin-releasing hormone ana­logues were added to the GH treatment in case of unsatisfactory final growth. Conclusions. Normal/high levels of GH and reduced IGF-1 are characteristic of children with BIGH syndrome. In addition, these children have a significant increase in ghrelin in the first hours after falling asleep. The test for sensitivity to GH is a reliable diagnostic method. Thyroid and adrenal disorders were not found in patients with BIGH syndrome. Children with BIGH syndrome have normal sexual development with a tendency to precocious puberty. The simultaneous use of gonadotropin-releasing hormone analogues in combination with GH preparations significantly improves patients’ final growth.

Metachromatic, tryptase- and ghrelin-positive mast cells in the blood vessels of rat’s lung

Mast cells and the mediators they release play a major role in the pathogenesis of lung diseases. They regulate the function of the smooth muscle layer of the pulmonary airways and the same layer of the blood vessels. There are no data about the distribution of metachromatic and tryptase-positive mast cells in the blood vessels’ wall as well as on the content of ghrelin in mast cell granules in rat’s lung. The aim of this research was to present an analysis of the number and localisation of tryptase-positive, ghrelin-positive and metachromatic mast cells in the blood vessels (arteries, capillaries, venules and veins) in rats of different age. Six male Wistar rats were used for each age group - 20 days, 3 months and 1 year. Tissue slices for histochemical examination were taken from the caudal lobe of the left lung and stained with toluidine blue. Immunohistochemical reactions were then performed to indicate the expression of tryptase and ghrelin, allowing comparing the presence of tryptase-, ghrelin-positive and metachromatic mast cells in the wall of the blood vessels of different diameters. The light microscopical study showed that in all types of blood vessels from the three age groups, the number of ghrelin positive cells was the largest, followed by tryptase-positive and metachromatic mast cells. The observed differences in the distribution of these cells are important for maintaining the lung homeostasis and can be used as reference values in experimental studies in order to obtain accurate results.

Effect of L-carnitine and resveratrol complex on the profile of cytokines and regulatory proteins in normal and obese rats

Chronic inflammation in adipose tissue, peripheral organs and some compartments of the brain are among pathogenetic factors in obesity. The use of bioactive compounds with anti-inflammatory and hypolipidemic activity in the composition of specialized products and dietary supplements is considered as an approach in the diet therapy of obesity and related conditions. The aim of the research was to study the effect of a complex supplement containing resveratrol and L-carnitine (RC supplement) on the immunological parameters of inflammation (the profile of cytokines and regulatory proteins) in rats fed a balanced or hypercaloric diet. Material and methods. Male Wistar rats received for 63 days a standard balanced diet (SD) or a high-carbohydrate-high-fat diet (HFCD) with an excess of total fat and fructose, as well as RC supplement at a low (25 mg/kg body weight as Res and 300 mg/kg body weight as L-Car) or high (50 and 600 mg/kg body weight, respectively) dose. The content of leptin, ghrelin, cytokines and chemokines in blood serum (BS), lysates of white adipose tissue (WAT) and spleen, amygdala and hippocampus of the brain, the content of regulatory proteins Akt, IRS-1, GCK-3a/b, p70/S6, BAD, m-TOR, PTEN and S6 ribosomal protein in the amygdala and hippocampus have been studied the by multiplex immunoassay. Results. In rats that consumed RC as part of SD, there was a decrease in the levels of leptin and its ratio with ghrelin, the levels of proinflammatory cytokines (TNF-α, IL-1α, IL-12p40 and IL-12p70, IFN-γ) in BS and WAT, chemokines (MCP-1, M-CSF, MIP-2) in WAT. Some of these effects were more pronounced at a low dose of RC than at a large dose, and some of them were also canceled or changed in direction in animals treated with HFCD. In the amygdala, RC consumption increased the content of both pro- and antiinflammatory cytokines; the most significant was the increase in IL-7 levels in animals fed SD, and RANTES in animals fed HFCD. In the hippocampus of rats, the RC intake had an insignificant effect on the levels of cytokines and chemokines. Akt-1 kinase and the substrate of the insulin receptor IRS-1 were the main targets of RC action in the regions of the brain. Conclusion. The complex dietary supplement RC exerted a hypoleptinemic effect, revealed certain anti-inflammatory effects and modulated a number of the brain factors influencing behavioral responses in obesity. However, the synergistic effect of resveratrol and L-carnitine in the composition of the supplement wasn't not observed, and the effectiveness of its action decreased in conditions of a hypercaloric diet consumption.

Ghrelin as a biomarker of non-motor symptoms and sleep disorders at Parkinson's disease

ABSTRACT. Among the movement disorders characterized by Parkinson's disease, an equally important component is non-motor symptoms. To date, the neurophysiological basis of development and potential biomarkers of the disease remain insufficiently studied. The purpose of our study is to analyze the possibility of using the level of ghrelin in blood plasma as a biomarker of non-motor symptoms and sleep disturbances in Parkinson's disease depending on circadian rhythms. We examined 64 patients with Parkinson's disease registered at the Center for Parkinson's Disease and Other Neurodegenerative Diseases, Department of Nervous Diseases, Poltava State Medical University, and 30 patients without signs of neurodegenerative disease. The diagnosis was established according to the criteria of the World Brain Bank of Great Britain. Non-motor manifestations were studied according to the results of the non-motor symptom assessment scale, the severity of sleep disorders was assessed according to the sleep scale at Parkinson's disease. Results. In the course of the study, a decrease in the level of ghrelin in the blood plasma and the connection of the ghrelin content with sleep and digestive system disorders in patients with Parkinson's disease were established. patients, which is consistent with other studies. Ghrelin stimulates motility and emptying of the stomach, as well as motility of the small and large intestines. This indicates the probable role of ghrelin in the pathophysiology of diseases of the digestive system at Parkinson's disease. Conclusions. The level of plasma ghrelin in patients with Parkinson's disease and its diurnal fluctuations can be considered as a potential biomarker of non-motor symptoms and their fluctuations due to its links with sleep disorders and circadian rhythm.

The Combinatory Effect of Spirulina Supplementation and Resistance Exercise on Plasma Contents of Adipolin, Apelin, Ghrelin, and Glucose in Overweight and Obese Men.

Methods The current investigation was conducted in a single-blind and quasiexperimental fashion. Sixty overweight and obese men (BMI > 25) ranging in age from 30 to 55 years were purposefully selected and randomly assigned to one of four groups: training plus spirulina (T+S), training plus placebo (T+P), spirulina (S), or placebo (P). For eight weeks, the (S) and (P) groups consumed two 500 mg spirulina and placebo capsules daily, respectively. Resistance training was performed three sessions a week over eight weeks, consisting of 12 movements with 1-, 2-, 3-, and 4-minute rest intervals and 40-90 percent maximal repetition. Adipolin, apelin, and ghrelin indices were measured before and after exercise using special kits. Results All variables changed significantly between groups except for apelin. Within-group comparisons revealed a substantial increase in adipolin levels in the (T+S) and (T+P) groups (P < 0.05). Apelin levels were decreased in the (T+S) and (T+P) groups. Additionally, FBS levels reduced significantly in (T+S) (P = 0.01). Conclusion It seems that eight weeks of circuit resistance training and spirulina supplementation can lead to reduced weight and apelin and FBS levels as well as increased concentrations of adipolin and ghrelin contents in overweight and obese men.

A highly effective and stable butyrylcholinesterase inhibitor with multi-faceted neuroprotection and cognition improvement

Butyrylcholinesterase (BChE) has been more and more attractive for treating neurodegenerative diseases, especially Alzheimer's disease (AD). In this study, we conducted activity and druggability optimization based on the structures that were previously reported. Most compounds exhibited pronounced BChE inhibitory capacity with nanomolar IC50 values. Based on the results of inhibiting activity and cyto-safety evaluations, two compounds (7, eqBChE IC50 = 2.94 nM, hBChE IC50 = 34.6 nM, and 20, eqBChE IC50 = 0.15 nM, hBChE IC50 = 45.2 nM) have been selected as candidates. High stability of compound 20 contributed to significantly improved blood concentration and tissue exposure, resulting in a reduced administration and effective dose in pharmacodynamic experiments. Two candidates exhibited remarkable neuroprotective properties and cognition improving activity, by benefiting cholinergic system, reducing the total Aβ amount and increasing the ghrelin content. Simultaneous modulation in the center and periphery greatly improves the efficiency of BChE inhibitors. Considering the regulation on ghrelin level, BChE inhibition could improve not only symptoms but also nutritional status of AD patients.

Changes in metabolic and hormonal profiles during transition period in dairy cattle \u2013 the role of spexin

BackgroundThis study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors – galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, β-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF–I, triglycerides, cholesterol, leptin, corticosterone and 17-β-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase.ResultsSpexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = − 0.39) and total ghrelin contents (r = − 0.41), weakly correlated with BHBA (r = − 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen).ConclusionA negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring.

Вміст греліну в плазмі крові дітей із синдромом біологічно неактивного гормона росту

Актуальність. У світовій літературі відомості про стан системи «гормон росту/ростові фактори» (ГР/інсуліноподібний фактор росту 1 (ІФР-1)), зокрема щодо відношень ГР/ІФР-1/грелін (Ghr), у пацієнтів із низькорослістю вкрай обмежені. Мета роботи — визначення особливостей секреції греліну в пацієнтів із синдромом біологічно неактивного гормона росту порівняно із секрецією греліну в дітей із соматотропною недостатністю. Матеріали та методи. Ghr визначали в 33 хворих із низькорослістю, серед них 22 пацієнти — із соматотропною недостатністю і 11 хворих — із синдромом біологічно неактивного гормона росту. Паспортний вік всіх обстежених пацієнтів відповідав діапазону статевого дозрівання. Кістковий вік в обох групах відставав від паспортного більше ніж на 2 роки. Відставання в рості всіх дітей становило від мінус 2SD. Контрольну групу становили 6 здорових дітей. У всіх обстежених дітей визначали базальний рівень ГР, ІФР-1 й рівень ГР під час нічного викиду та стимуляційного тесту з клонідином. Одночасно отримували зразки крові для дослідження рівня Ghr. Результати. Найсуттєвіші зміни показників рівня Ghr були виявлені через 120 хвилин після засинання у всіх обстежених. Установлено значне підвищення рівня Ghr у дітей із синдромом біологічно неактивного гормона росту, соматотропною недостатністю, а також у групі контролю порівняно з базальними показниками та максимальним викидом при проведенні клонідинового тесту. Так, нічний рівень Ghr перевищував базальний в 1,4 раза в дітей із соматотропною недостатністю, у 3,4 раза — у дітей із синдромом біологічно неактивного гормона росту та у 2,8 раза — у дітей контрольної групи. Ми не встановили зв’язку між показниками ІФР-1 та Ghr у всіх обстежених дітей. Висновки. У пацієнтів із синдромом біологічно неактивного гормона росту та соматотропною недостатністю встановлено суттєвий викид греліну в перші години після засинання. Не виявлено взаємозв’язку між рівнями греліну та ІФР-1 у пацієнтів із синдромом біологічно неактивного гормона росту, соматотропною недостатністю та в здорових дітей. Введення клонідину не викликає суттєвих змін рівня греліну в низькорослих та здорових дітей.

Вміст греліну та лептину в плазмі крові в дітей та підлітків із дисфункцією гіпоталамуса

Мета дослідження — проведення порівняльного аналізу рівнів лептину та греліну в плазмі крові дітей і підлітків залежно від форми та ступеня ожиріння на тлі дисфункції гіпоталамуса. Матеріали та методи. Обстежено 39 дітей віком від 10 до 18 років із дисфункцією гіпоталамуса. Серед них 16 пацієнтів (41,03 %) — із вісцероабдомінальним ожирінням, 23 пацієнти (58,97 %) — із глютеофеморальним ожирінням та 14 здорових дітей відповідного віку та статі. У всіх пацієнтів проводили вивчення анамнезу життя, оцінку антропометричних параметрів (маса тіла, індекс маси тіла, окружність талії та стегон, їх співвідношення). Рівень лептину у крові визначали імуноферментним методом із використанням наборів фірми Roche Diagnostics GmbH Mannheim (Німеччина). Рівень греліну визначали радіоімунологічним методом із використанням наборів фірми DLAsource ImmunoAssays S.A. (Бельгія). Результати. Надлишкова маса тіла встановлена у 15 із 39 пацієнтів (38,5 %), ожиріння I ступеня — у 8 дітей (20,5 %), II ступеня — у 10 дітей (25,6 %), III ступеня — у 6 дітей (15,4 %). Середній рівень лептину в дітей із вісцероабдомінальним ожирінням становив 47,20 ± 5,54 нг/мл (індекс маси тіла — 35,20 ± 5,07 кг/м2) і виявився вірогідно вищим, ніж у дітей у групі з глютеофеморальним ожирінням (26,50 ± 7,13 нг/мл, p &lt; 0,05) у поєднанні з аналогічними метаболічними порушеннями. Рівень греліну в дітей з ожирінням був вірогідно нижчим, ніж у контрольній групі, і залежав від ступеня ожиріння. При ожирінні III ступеня рівень греліну був найнижчим — 582,58 ± 59,37 нг/мл. Висновки. Ожиріння на тлі дисфункції гіпоталамуса в дітей та підлітків супроводжується низьким рівнем греліну та високим рівнем лептину в плазмі крові. Незалежно від статі в дітей і підлітків гіперлептинемія та гіпогрелінемія значною мірою пов’язані зі ступенем та формою ожиріння. При вісцероабдомінальній формі ожиріння (порівняно з глютеофеморальною формою) зафіксовано істотно нижчий рівень греліну та вищий рівень лептину.

Ammonia exposure causes the imbalance of the gut-brain axis by altering gene networks associated with oxidative metabolism, inflammation and apoptosis

Ammonia is an acknowledged environment pollutant in atmosphere with irritating smell. Previous studies have shown that excessive ammonia has toxic effects on farm animals and humans. However, the detail toxicity mechanism of ammonia to pigs is still unknown so far. In order to clarify the mechanism of ammonia toxicity, we established a porcine exogenous ammonia poisoning model and assessed the effects of ammonia on the gut-brain axis by transcriptome sequencing, histological observation and chemical analysis. Our results showed that after 30 d of ammonia exposure, 578 differentially expressed genes (DEGs) and 407 DEGs were obtained in the hypothalamus and jejunum, respectively. These DEGs were enriched into Gene Ontology terms associated with inflammation, oxidative metabolism, apoptosis, and the highly expressed genes among these DEGs were verified by real-time quantitative PCR. The content of glutathione and the activities of glutathione peroxidase and superoxide dismutase were significantly decreased, while malondialdehyde content was increased after ammonia exposure. Corticotropin releasing factor, substance P, 5-hydroxytryptamine and ghrelin contents in serum elevated significantly. Furthermore, pathologic observation in the ammonia group revealed infiltration of lymphocytes in the hypothalamus and significant decrease of jejunal epithelial cells. Our results indicated that ammonia exposure mediated changes in transcriptional profiles, pathological damage, oxidative stress and brain-gut peptide of the pig jejunum and hypothalamus, and induced the imbalance of the brain-gut axis through the “oxidative stress-inflammation-apoptosis” interaction network. Our study not only provides a new perspective for the toxicity assessment of ammonia, but also enriches the toxicology mechanism of ammonia.

The Ciji-Hua'ai-Baosheng II Formula Attenuates Chemotherapy-Induced Anorexia in Mice With H22 Hepatocellular Carcinoma.

Background: Ciji-Hua’ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medicine formula, which specifically targets different aspects of chemotherapy-induced adverse effects in patients with cancer. In our clinical application, CHB-II-F significantly alleviated chemotherapy-induced anorexia (loss of appetite) and improved the quality of life for patients with tumor during and after chemotherapy. However, the mechanism of CHB-II-F in alleviation of chemotherapy-induced anorexia remains to be further investigated.Aim of Study: To explore the therapeutic effect and mechanism of CHB-II-F on chemotherapy-induced anorexia in the mice model of H22 hepatoma.Materials and Methods: A total of 72 Kunming mice of SPF grade were inoculated subcutaneously with H22 hepatoma cells into the right anterior armpit of the mice. After 1 week of seeding, mice were injected intraperitoneally with a high dose of 5-fluorouracil (200 mg/kg 5-FU) to establish the model of chemotherapy. The mice were randomly divided into six groups: untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji capsule (YZXJC) group, and three groups of 5-FU plus different concentrations of CHB-II-F. All the mice in each group were treated for 14 days. The body weight, food intake, tumor volume, and tumor weight of mice were measured, and pathological examinations of tumor tissue, stomach, and duodenum were carried out. Expressions of serum Leptin, Neuropeptide Y (NPY), epidermal cell growth factor (EGF), Motilin (MTL), Orexin A (OXA), Gastrin (GAS), Ghrelin, Prostaglandin E2 (PGE2), and jejunum superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined. The protein and mRNA levels of proopiomelanocortin (POMC), Orexin receptor 1 (OX1R), neuropeptide Y (NPY), cocaine and amphetamine regulated transcript peptide (CART), Agouti gene-related protein (AgRP), Leptin receptor (Ob-R), and Ghrelin receptor (GHSR) were examined in hypothalamus, and the protein levels of substance P (SP) and 5-hydroxytryptamine (5-HT) in duodenum were measured.Results: The combination of CHB-II-F and 5-FU could enhance the inhibitory effect of 5-FU on tumor. The tumor inhibition rates of 5-FU group, YZXJC group, CHB-II-F(H) group, CHB-II-F(M) group, and CHB-II-F(L) group were 58.88, 28.08, 54.96, 37.69, and 28.61%, respectively. Compared with untreated group and 5-FU group, CHB-II-F significantly increased the body weight and food intake of tumor-bearing mice; increased the content of NPY, Orexin A, Ghrelin, GAS, MTL, EGF, and PGE2 in serum and the activity of SOD in jejunum; and decreased the content of Leptin in serum and the content of MDA in jejunum. Compared with untreated group and 5-FU group, CHB-II-F also enhanced the expression of OX1R, GHSR, NPY, and AgRP protein and gene and decreased the expression of Ob-R, POMC, and CART protein and gene in hypothalamus of mice, and the gene expression was consistent with the protein expression. In addition, CHB-II-F decreased the expression of 5-HT and SP protein in duodenum.Conclusion: In the murine model of H22 hepatocellular carcinoma (HCC) receiving chemotherapy, CHB-II-F enhances the inhibitory effect of 5-FU on tumor, significantly improves the pathological injury of gastrointestinal tract caused by chemotherapy, and regulates the secretion of gastrointestinal hormones. It may alleviate chemotherapy-induced anorexia by affecting appetite regulatory factors in the feeding area of hypothalamus central nervous system and peripheral appetite regulatory factors.

Reactive changes of gastric mucosa and reduction of desacyl grelin in rat brain due to psychoemotional stress

BACKGROUND: The work is devoted to the analysis of the elements the reactivity of grelin system in the model of psychogenic stress. In recent years, it has been shown that the ghrelin brain system is not limited only to the regulation of energy balance and eating behavior. Along with other peptide regulatory systems, it plays an important role in the mechanisms of stress, reward and addiction. Therefore, the elements of this system should be considered primarily as molecular targets of pharmacological action in order to correct the states of addiction and post-stress disorders.&#x0D; MATERIALS AND METHODS: To produce psychoemotional stress, we used an acute single traumatic situation in male Wistar rats. The animals were placed in the tiger python, one animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. One week after exposure to python, the animals were decapitated, and the brain structures were isolated. Aliquots of the brain structures suspensions were examined for the content of desacyl ghrelin (DAG) using a highly sensitive enzyme-linked immunosorbent assay (ELISA). In another group, rats were decapitated on the 4th day after exposure to python, stomachs were removed, which were fixed in 10% formalin solution. In horizontal paraffin sections of the gastric mucosa, after staining with hematoxylin and eosin, the heights of superficial and dimple mucous cells, the height of the dimple stroma, the area of superficial, dimple mucocytes and stroma of the dimples, and the number of dead mucocytes were calculated. To clarify the differentiation of epithelial cells, they were stained with alcian blue&#x0D; RESULTS: DAG was detected in all studied brain structures: amygdala, hippocampus, and hypothalamus. The highest concentration of DAG was noted in the hypothalamus (p 0.05), which may serve as an indirect confirmation of the data on the presence of ghrelin-containing neurons in the nuclei of the hypothalamus. After exposure to stress, a sharp decrease in the level of DAG was observed in all studied brain structures (812 times, p 0.01): amygdala, hippocampus, and hypothalamus. It has been established that the experience of the stress of the death of a partner is expressed by erosive inflammation of the gastric mucosa, the death of many mucous cells, and an increase in mucus production in viable epithelial cells.&#x0D; CONCLUSION: Psychoemotional stress completely suppresses the content of desacyl ghrelin of the brain in rats, which may be based on both a disturbance of the central mechanisms of limbic regulation and a violation of peripheral mechanisms, in particular, reactive changes in the gastric mucosa.

High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development.

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

Pathogenetic mechanisms for the development of hematological disorders in induced fatty liver disease in Wistar rats and assessment of the regulatory effects of carnosine and α-lipoic acid

The study of the relationship between hematopoiesis and metabolism is now particularly relevant in view of the high incidence of alimentary dependent diseases, including non-alcoholic fatty liver disease. In this regard, pathogenetic factors of this disease development are studied actively in order to choose adequate drug therapy and usage of bioactive substances with antioxidant properties. The aim of the study was to study the pathogenetic relationship of hematological disorders and imbalance of growth factors, leptin and ghrelin in male Wistar rats in the model of the initial stage of non-alcoholic fatty liver disease development and to assess the regulatory effect of minor bioactive substances - carnosine and α-lipoic acid. Material and methods. The studies were performed on male Wistar rats with initial body weight 150±10 g within 8 weeks. Animals were divided into 5 groups (n=8 in each). Rats of the control group received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the combined addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. Hematological values were determined on a hematological analyzer. The content of ghrelin and leptin, as well as growth factors GM-CSF and M-CSF in blood plasma and adipose tissue lysates, was determined by multiplex immunoassay using xMAP technology. Results. Rat intake of HCCDD resulted in decreased hemoglobin levels and red blood cell scores compared to controls. Diet enrichment with carnosine and α-lipoic acid did not have a reliable effect on these indicators. Carnosine intake had a protective effect on erythrocyte volume, a decrease of which was recorded in other experimental groups. HCCDD stimulated the growth of the absolute number of leukocytes in peripheral blood due to granulocytes and mononuclears. The enrichment of HCCDD with carnosine and α-lipoic acid led to a further increase in leukocytosis, the maximum level of which was observed in the group of rats fed HCCDD, simultaneously enriched with carnosine and α-lipoic acid (14.86±1.48×109/l compared to 8.67±1.23×109/l in control). All diets used in the research had no effect on the number of erythrocytes and platelets in the peripheral blood of rats. The use of both HCCDD alone and in combination with carnosine or α-lipoic acid intake had a negative effect on the level of growth factors GM-CSF and M-CSF in blood plasma and adipose tissue. The consumption of HCCDD caused an increase in leptin blood level (8.54±0.69 compared to 2.58±0.37 pg/ml in control, р<0.05), which was normalized by enriching the diet with carnosine and α-lipoic acid. Ghrelin blood level significantly decreased in all experimental groups compared to the control: by 30% in rats fed and by almost 50% when carnosine and α-lipoic acid were added to HCCDD. The intake of α-lipoic acid led to hormone level changes in adipose tissue lysates, leptin content decreased (2.31±0.11 vs 2.77±0.15 pg/ml), while ghrelin level significantly increased (0.35±0.14 vs 0.20±0.06 pg/ml), compared with the control group (р<0.05). Conclusion. The revealed interrelation of parameters of the cellular composition of peripheral blood and hemoglobin content with the changes in the content of GM-CSF, M-CSF, leptin and ghrelin in blood plasma and adipose tissue indicates the mutual influence of the studied CSF, leptin, ghrelin and added antioxidants (carnosine and α-lipoic acid) on the regulatory mechanisms of hematopoiesis in rats fed HCCDD.

Effects of Stimulating Local and Distal Acupoints on Diabetic Gastroparesis: A New Insight in Revealing Acupuncture Therapeutics.

One of the most important aspects of clinical acupuncture practice, like diabetic gastroparesis, is the selection of suitable acupoints. Furthermore, it is critical to examine the therapeutic impact differences between distal and local acupoints, as well as the prescription of their combination. In this study, diabetic gastroparesis rats were treated by needling Zhongwan (CV12) and Zusanli (ST36), and then used Single Photon Emission Computed Tomography-CT (SPECT-CT) technology to assess the effects of promoting gastric motility. In addition, morphological observation, immunohistochemical examination, and biomarker assays, such as determination of growth factor 1, motilin, and ghrelin contents in serum samples, were performed to better understand the impact of certain various acupuncture treatments. All of the therapies improved the symptoms of diabetic gastroparesis rats, according to the findings. Stimulating these acupoints, on the other hand, can have a different therapeutic effect. In addition, needling local and distal acupoints together can have an antagonistic or synergistic impact on specific physiological and biochemical indexes such as gastric motility, ghrelin, gastrin, and growth factor 1, among others. Our findings demonstrated the benefits of acupoints and acupuncture in the management of diabetic gastroparesis, as well as a new insight into acupuncture therapeutics.

Ghrelin inhibited pressure overload–induced cardiac hypertrophy by promoting autophagy via CaMKK/AMPK signaling pathway

Ghrelin, a novel gut hormone, has been shown to exert protective effects on cardiac dysfunction and remodeling. However, the underlying mechanisms of its protective effects remain unclear. Here, we investigated the effects of ghrelin on cardiac hypertrophy and explored the mechanisms involved. Ghrelin (30 μg.kg−1. day−1) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini-osmotic pump the next day after surgery continuously for 4 weeks. The AAC treated rats without ghrelin infusion showed decreased ghrelin content and expression of its receptors in the hearts. Exogenous ghrelin greatly attenuated cardiac hypertrophy as shown by heart weight to tibial length (HW/TL), hemodynamics, echocardiography, histological analyses, and expression of hypertrophic markers induced by AAC. This corresponded with decreased cardiac fibrosis and inflammation in the hearts of AAC rats treated with ghrelin. Moreover, ghrelin significantly increased the myocardial expression of autophagy markers, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by ghrelin, which was reversed by inhibition of autophagy. The enhancement of autophagy and inhibition of apoptosis by ghrelin were eliminated on pretreatment with compound C, an AMP-activated protein kinase (AMPK) inhibitor. Furthermore, inhibition of Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), an upstream kinase of AMPK, made ghrelin fail to activate AMPK and simultaneously reversed ghrelin’s promotion of autophagy. In conclusion, ghrelin could exert its cardioprotective effects on cardiac hypertrophy by promoting autophagy, possibly via CaMKK/AMPK signaling pathway.

Effects of Progressive Aerobic Training on Serum and Gastric Acylated Ghrelin, IGF-1 and Body Weight in Female Rats

Background: It is generally believed that physical activity can lead to increased food intake, whereas some studies state that exercise can have inhibitory effects on appetite and calorie intake. Objectives: The purpose of this study was to examine the changes in the level of gastric and serum ghrelin, body weight, and serum IGF-1 after a period of progressive aerobic training (PAT) in female rats. Methods: After one week of familiarization with treadmill running, 16 adult female rats were randomly assigned to two groups: control (n = 8) and aerobic exercise (n = 8). The exercise protocol consisted of progressive aerobic running on the treadmill for three months (5 days a week). Forty-eight hours after the last exercise session, the animals were sacrificed. Serum levels of ghrelin, IGF-1, and ghrelin content in the gastric tissue were measured using the ELISA method. An Independent t-test was used for comparison of data between the two groups. Results: The results indicated that three months of PAT had no significant effect on gastric (P = 0.51) and serum acylated ghrelin (P = 0.15), weight changes (P = 0.42), and serum IGF-1 (P = 0.56) compared to the control group. Conclusions: Three months of PAT in female animals had no effects on ghrelin level, food intake and weight loss, and serum IGF-1 level. It seems that there are sex-specific hormonal and appetite responses to progressive aerobic training.

Correlations between immune and metabolic serum markers and schizophrenia/bipolar disorder polygenic risk score in first-episode psychosis.

There is a strong interest in identifying the biological mechanisms involved in the genetic risk for psychotic disorders. In this study, we evaluated the correlation between serum concentrations of specific molecular markers and the genetic component for schizophrenia and bipolar disorder. We analysed the association between the polygenic risk score (PRS) and the serum levels of different inflammatory/metabolic markers in a sample of 81 first-episode psychosis patients (FEP) with a diagnosis of schizophrenia or bipolar disorder and 33 controls. A positive correlation of schizophrenia and bipolar disorder PRS with the inflammatory marker C-C Motif Chemokine Ligand 4 serum concentration (ρ = 0.42, P = 1.56 × 10-04 and ρ = 0.40, P = 1.65 × 10-03 , respectively) and a negative correlation with the serum ghrelin content (ρ = - 0.35, P = 4.27 × 10-03 and ρ = - 0.45, P = 6.05 × 10-04 , respectively) were observed. These findings provide new insight into the biological underpinnings of the PRS component, thus supporting a role of the genetic liability on the inflammatory and metabolic alterations that characterize psychosis onset.

The role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesity

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion. AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes. MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m 2 )and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m 2 ) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software. RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml. CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content.