Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia / 中国针灸

OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD.@*METHODS@#A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats.@*RESULTS@#In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group.@*CONCLUSIONS@#Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome / 中国中药杂志

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

Short sleep duration is associated with high energy and total lipid intake in obese women: a pilot study / A curta duração do sono está associada ao elevado consumo energético e de lipídios totais em mulheres com obesidade: um estudo piloto

ABSTRACT Objective To evaluate the influence of self-reported sleep duration on ghrelin secretion and nutritional indicators in obese women. Methods This is an observational study, including 36 adult women with obesity. Sleep duration was reported while completing the general questionnaire. Dietary, laboratory, anthropometric, and body composition indicators, and resting metabolic rate, were evaluated. For statistical analysis, sleep duration data were grouped into tertiles: less than six (first tertile); equal to or above six; and less than eight (second tertile); equal to or greater than eight hours of sleep per day (third tertile). The indicators were compared for the different ranges of the sleep duration. Results There was no significant difference when comparing anthropometric, laboratory, and energy expenditure indicators between sleep tertiles. However, women with shorter sleep duration (less than 6 hours per day) had a higher mean caloric intake, compared with the tertile of eight hours or more of sleep per day. For total lipid intake, the mean consumption was higher in the first tertile (up to six hours a day). Conclusion Sleeping less than six hours a day led to an increase in energy and lipid intake in obese women. However, it did not change the plasma ghrelin concentration.

RESUMO Objetivo Avaliar a influência da duração de sono autorrelatada na secreção de grelina e indicadores nutricionais na obesidade. Métodos Trata-se de um estudo observacional, incluindo 36 mulheres adultas com obesidade. A duração do sono foi relatada durante o preenchimento do questionário de dados gerais. Foram avaliados indicadores dietéticos, laboratoriais, antropométricos e de composição corporal, além da taxa metabólica de repouso. Para análise estatística, os dados de duração de sono foram agrupados em tercis, sendo menor do que seis (primeiro tercil), igual ou acima seis e menor do que oito (segundo tercil), igual ou maior do que oito horas de sono por dia (terceiro tercil). Os indicadores supracitados foram comparados entre as diferentes faixas dos tercis de duração de sono. Resultados Não houve diferença significativa ao comparar os indicadores antropométricos, laboratoriais e do gasto de energia, entre os tercis de sono. Porém, mulheres com menor tempo de duração do sono (menos de 6 horas por dia) apresentaram maior média da ingestão calórica, comparado com o tercil de oito horas ou mais de sono por dia. Para a ingestão de lipídios totais, a média de consumo foi maior no primeiro tercil (até seis horas por dia). Conclusão Dormir menos do que seis horas por dia levou ao aumento na ingestão energética e de lipídios em mulheres com obesidade, porém, não alterou a concentração de grelina plasmática.

Fasting levels of appetite regulating hormones predict caloric intake at breakfast in a group of Chilean adolescents / Los niveles en ayunas de hormonas reguladoras del apetito predicen la ingesta energética en el desayuno en adolescentes

BACKGROUND: Appetite regulation is integral to food intake and is modulated by complex interactions between internal and external stimuli. Hormonal mechanisms which stimulate or inhibit intake have been characterized, but the physiologic effects of serum levels of such hormones in short-term appetite regulation have received little attention. AIM: To evaluate whether fasting levels of orexigenic/anorexigenic hormones were associated with energy intake at breakfast, served soon after drawing a fasting blood sample, in a group of adolescents. MATERIAL AND METHODS: Anthropometry, body composition and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured in 655 Chilean adolescents aged 16.8 ± 0.3 years (52% males). Energy intake was measured at a semi-standardized breakfast. Associations between hormone levels and energy intake were studied using multivariate linear models. RESULTS: Thirty nine percent of participants were overweight/ obese. After an overnight fast, median values for leptin, insulin, ghrelin and orexin-A were 7.3 ng/mL, 6.7 IU/dL, 200.8 pg/mL, and 16.1 pg/mL, respectively. Participants ate on average 637 ± 239 calories at breakfast. In multivariable models, insulin levels were inversely and independently associated with caloric intake at breakfast (β = −18.65; p < 0.05), whereas leptin, ghrelin and orexin-A levels were positively and independently associated with intake: β= 5.56, β = 0.34 and β = 8.40, respectively, p < 0.05. CONCLUSIONS: Fasting leptin, ghrelin and orexin-A were positively associated with energy intake during breakfast provided soon after the blood draw. Insulin was negatively associated with energy intake. Modifiable factors influencing levels of appetite regulating hormones could be a potential target for influencing food intake.

ANTECEDENTES: La regulación del apetito es parte integral de la ingesta alimentaria y es modulada por complejas interacciones entre estímulos internos y externos. Se han caracterizado los mecanismos hormonales que estimulan o inhiben la ingesta, pero los efectos fisiológicos de los niveles séricos de tales hormonas en la regulación del apetito a corto plazo han recibido poca atención. OBJETIVO: Evaluar si los niveles en ayunas de hormonas orexigénicas/ anorexigénicas se asocian con la ingesta energética en el desayuno, entregado inmediatamente después de una muestra de sangre en ayunas, en un grupo de adolescentes. MATERIAL Y MÉTODO: Se efectuaron mediciones antropométricas, composición corporal y medición de niveles en ayunas de leptina, insulina, grelina y orexina-A en 655 adolescentes de 16,8 ± 0,26 años. La ingesta energética se midió en un desayuno semiestandarizado. Se estudiaron las asociaciones entre los niveles hormonales y la ingesta energética mediante modelos lineales multivariados. RESULTADOS: Los valores de leptina, insulina, grelina y orexina-A fueron 7,3 ng/mL, 6,7 UI/dL, 200,8 pg/mL y 16,1 pg/mL respectivamente. Los participantes comieron un promedio de 637 ± 239 calorías en el desayuno. Los niveles de insulina se asociaron inversa e independientemente con la ingesta del desayuno (β = −18,65; p < 0,05), mientras que los niveles de leptina, grelina y orexina-A se asociaron positiva e independientemente con la ingesta: β = 5,65; β = 0,34; β = 8,40, (p < 0,05). CONCLUSIONES: La leptina, grelina y orexina-A en ayunas se asociaron positivamente con la ingesta de energía durante el desayuno proporcionado poco después de la muestra de sangre. La insulina se asoció negativamente con la ingesta de energía. Los factores modificables que influyen en las hormonas reguladoras del apetito podrían ser un objetivo potencial para influir en la ingesta de alimentos.

Association between functional dyspepsia and serum levels of brain-gut peptides in children / 中国当代儿科杂志

OBJECTIVES@#To study the association between functional dyspepsia (FD) and serum levels of brain-gut peptides including calcitonin gene-related peptide (CGRP), nesfatin-1, and ghrelin in children.@*METHODS@#A total of 38 children with FD who attended Shengjing Hospital of China Medical University from November 2019 to December 2020 were enrolled as the FD group. Thirty-four healthy children were enrolled as the control group. Serum samples were collected from all of the children. Enzyme-linked immunosorbent assay was used to measure serum levels of CGRP, ghrelin, and nesfatin-1 for comparison between the two groups. The scores of clinical symptoms were determined for the children with FD. Spearman rank correlation analysis was used to investigate the correlation of symptom scores with the serum levels of brain-gut peptides.@*RESULTS@#The FD group had significantly higher serum levels of nesfatin-1 and CGRP than the control group (P<0.05), while there was no significant difference in the serum level of ghrelin between the two groups (P>0.05). The serum level of nesfatin-1 was positively correlated with the symptom score of early satiety (rs=0.553, P<0.001), but was not significantly correlated with the total score of FD (rs=0.191, P=0.250). The serum level of CGRP was positively correlated with the scores of abdominal pain (rs=0.479, P=0.002) and belching (rs=0.619, P<0.001) and the total score of FD (rs=0.541, P<0.001).@*CONCLUSIONS@#CGRP and nesfatin-1 may play an important role in the pathophysiological process of FD.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Effects of exogenous ghrelin on the tissue structure and somato-statin secretion in the pancreas of African ostrich chicks / Efectos de la grelina exógena en la estructura del tejido y la secreción de somato-estatinas en el páncreas de los polluelos de avestruz africanos

SUMMARY: This study aimed to investigate the effect of exogenous ghrelin on pancreatic growth and development in African ostrich chicks. Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously metatarsal vein with saline (control) or ghrelin (10, 50, and 100 μg/kg) for 6 days. Body and pancreas weight were determined, structural characteristics were observed using HE staining, somatostatin-immunopositive cells were detected using immunohistochemistry. The results were as follows: 1. The 50 and 100 μg/kg groups showed lower relative pancreas weight than the control group (P 0.05. Moreover, compared with the control, the islet cells in treatment groups were loosely arranged and showed reduced cytoplasm. In the exocrine pancreas, the volume of acinar cells in the 10, 50, and 100 μg/kg groups all decreased to varying degrees. 3. Somatostatin immunopositive cells were mainly located around the periphery of the islets and sporadically distributed in the center. The density of the somatostatin immunopositive cells in the 10, 50, and 100 μg/kg groups was higher than that in the control (P < 0.05). These findings suggest that exogenous ghrelin increases the area and number of islets and number of somatostatin immunopositive cells but reduces relative pancreas weight and effects the morphological and structural development of the pancreas, which may inhibit the pancreatic growth and development in African ostrich chicks.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de la grelina exógena sobre el crecimiento y desarrollo del páncreas en polluelos de avestruz africana. Dieciséis pollos de avestruz africana de 40 días (machos o hembras) se dividieron al azar en cuatro grupos y se inyectaron por vía intravenosa con solución salina (control) o grelina (10, 50 y 100 μg / kg) durante 6 días. determinadas, se observaron las características estructurales mediante tinción Hematoxilina-Eosina, se detectaron células inmunopositivas a somatostatina mediante inmunohistoquímica. Los resultados fueron los siguientes: ¨Los grupos de 50 y 100 μg / kg mostraron un menor peso relativo del páncreas que el grupo de control (P <0,05). El área de islotes por unidad de área del páncreas fue mayor en los grupos de 10, 50 y 100 μg / kg grupos que en el grupo de control (P <0,05). El número de islotes por unidad de área del páncreas fue menor en el grupo de 10 μg / kg que en el control (P <0,05). Además, en comparación con el control, las células de los islotes en los grupos de tratamiento estaban dispuestas de forma holgada y mostraban un citoplasma reducido. En el páncreas exocrino, el volumen de células acinares en los grupos de 10, 50 y 100 μg / kg disminuyó en diversos grados. Las células inmunopositivas de somatostatina se ubicaron principalmente alrededor de la periferia de los islotes y se distribuyeron esporádicamente en el centro. La densidad de las células inmunopositivas a la somatostatina en los grupos de 10, 50 y 100 μg / kg fue mayor que la del control (P <0,05). Estos hallazgos sugieren que la grelina exógena aumenta el área y el número de islotes y el número de células inmunopositivas a la somatostatina, pero reduce el peso relativo del páncreas, lo que puede inhibir el crecimiento y desarrollo pancreático en los polluelos de avestruz africana.

Níveis de grelina circulante e a suscetibilidade ao câncer colorretal / Circulating ghrelin levels and susceptibility to colorectal câncer

ABSTRACT BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 controls were enrolled in this study. Plasma levels of ghrelin, insulin, and glucose were measured in all the subjects using ELISA and glucose oxidase methods. Furthermore, insulin resistance was assessed by calculating HOMA-IR index. RESULTS: The cases with CRC had decreased ghrelin levels (P<0.001) and a higher HOMA-IR index (P<0.001) than controls. Interestingly, when CRC patients were stratified based on tumor site, lower ghrelin levels and a higher HOMA-IR index were observed in the patients with either colon or rectal cancer vs. controls too. Additionally, there were an age and BMI-independent negative correlation between ghrelin levels and HOMA-IR (r=-0.365, P<0.05), and an age-independent negative correlation between ghrelin levels and BMI (r=-0.335, P<0.05) in the rectal subgroup. CONCLUSION: Our findings support a role for ghrelin in connection with insulin resistance and obesity in CRC susceptibility; however, it needs to be corroborated by further studies.

RESUMO CONTEXTO E OBJETIVO: Considerando a associação entre câncer colorretal (CCR), a resistência à insulina, à obesidade e o papel proeminente da grelina nessas doenças metabólicas, foi explorado se os níveis plasmáticos de grelina estavam associados ao CCR. Além disso, nos pacientes com CCR foram pesquisadas as possíveis correlações entre a grelina, insulina, resistência insulínica e índice de massa corporal (IMC) como indicadores de obesidade. MÉTODOS: Foram incluídos neste estudo 170 indivíduos, sendo 82 com CRC e 88 controles. Os níveis plasmáticos de grelina, insulina e glicose foram medidos em todos os sujeitos utilizando métodos ELISA e glicose oxidase. Além disso, a resistência à insulina foi avaliada pelo cálculo do índice HOMA-IR. RESULTADOS: Os pacientes com CRC apresentaram redução dos níveis de grelina (P<0,001) e maior índice HOMA-IR (P<0.001) do que os controles. Curiosamente, quando os pacientes com CRC foram estratificados com base no local do tumor, níveis mais baixos de grelina e maior índice de HOMA-IR foram observados nos indivíduos com câncer de cólon ou retal versus controles também. Além disso, houve uma correlação negativa entre idade e IMC independente entre os níveis de grelina e HOMA-IR (r=-0,365, P<0,05) e uma correlação negativa independente da idade entre os níveis de grelina e IMC (r=-0,335, P<0,05) no subgrupo retal. CONCLUSÃO: Nossos achados apoiam o papel da grelina em relação à resistência à insulina e à obesidade na suscetibilidade do CRC; no entanto, ela precisa ser corroborada por estudos posteriores.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

A single session of low-volume high-intensity interval and moderate-intensity continuous exercise elicits a transient reduction in ghrelin levels, but not in post-exercise energy intake in obese men

ABSTRACT Objective: This study investigated the acute effects of high-intensity interval (HIIE) and moderate-intensity continuous (MICE) exercise on ghrelin levels in obese men. Subjects and methods: A total of 10 obese men (age 27.6 ± 1.8 years, body mass index 35.4 ± 4.5 kg/m², body fat 39.9 ± 2.1%) performed two exercise sessions in a randomized order: HIIE (10 × 1 min intervals at 90% of the maximal heart rate [HRmax] interspersed by 1 min of active recovery) and MICE (20 min at 70% of the HRmax). Ghrelin levels were assessed pre-, post- and 1h post-exercise, and energy intake was assessed 1h post-exercise through an ad libitum meal. Results: HIIE and MICE showed a trend to decrease ghrelin levels immediately post-exercise (-14.1 ± 21.6% and −9.6 ± 23.8%, respectively, p = 0.07) and decreased 1h post-exercise (-12.7 ± 31.8% and −13.8 ± 21.7%, respectively, p < 0.05). No changes were observed for post-exercise energy intake (p > 0.05). There was a positive correlation between the change in ghrelin levels and post-exercise energy intake only for HIIE (r = 0.63, p = 0.05). Conclusion: In summary, a single session of HIIE and MICE elicits a reduction on ghrelin levels without changing post-exercise energy intake in obese men.

Comparación del tipo de cirugía bariátrica sobre la reducción de peso corporal y su relación con la ghrelina / Comparison between type of bariatric surgery on reduction of body weight and its ghrelin relationship

Resumen Objetivo: La cirugía bariátrica es un procedimiento para disminuir de peso a largo plazo en pacientes con obesidad. El objetivo de este estudio fue evaluar los niveles de ghrelina y la reducción del peso de acuerdo al tipo de cirugía bariátrica, comparando el bypass de una sola anastomosis y la gastrectomía formadora de manga. Materiales y Métodos: Estudio de cohorte que incluyó a 50 pacientes con obesidad, 22 mini-bypass y 28 mangas gástricas. Se evaluó el peso corporal y las concentraciones de ghrelina en la etapa prequirúrgica, en el día 7 y en los meses 1, 3 y 6 después de la cirugía. Resultados: Del total de pacientes, el 86% presentaron > 50% pérdida del exceso de peso (PEPP) a los 6 meses. La concentración de ghrelina disminuyó desde la primera semana en el grupo total de participantes. A los 6 meses, se observó mayor reducción de ghrelina en los pacientes con la manga gástrica (4.636 ± 2.535 vs 1.340 ± 1.001 pg/mL, p < 0,0001). El PEPP en pacientes con mini-bypass fue superior, en comparación con manga gástrica. Conclusiones: La comparación entre las técnicas indicó que, a los 6 meses de evolución posquirúrgica, los pacientes con mini-bypass presentaron mayor reducción de peso corporal y del nivel de ghrelina, en comparación con el grupo de manga gástrica. La concentración de ghrelina es una variable que participa en el control de peso; sin embargo, el tipo de abordaje quirúrgico probablemente tiene mayor relación con la pérdida de peso en estos pacientes.

Introduction: Bariatric surgery is a procedure to reduce weight in the long term in patients with obesity. The objective of this study was to evaluate ghrelin levels and weight reduction according to the type of bariatric surgery, comparing the single anastomosis bypass and the sleeve-forming gastrectomy. Materials and Method: Cohort study that included 50 patients with obesity, 22 Mini-Bypass and 28 gastric sleeve. Body weight and ghrelin concentrations were evaluated in the presurgical stage, on day 7 and in months 1, 3 and 6 after surgery. Results: Of the total of patients, 86% had > 50% excess weight loss (PEPP) at 6 months. The concentration of ghrelin decreased within the first week of the intervention. At 6 months, greater reduction of ghrelin was observed in patients with gastric sleeve (4636 ± 2535 vs 1340 ± 1001 pg/mL, p < 0.0001). The PEPP in patients with Mini-Bypass was superior, compared to gastric sleeve. Conclusion: The comparison between the techniques indicated that, after 6 months of post-surgical evolution, patients with Mini-Bypass had a greater reduction in body weight and ghrelin levels, compared to the gastric sleeve group. Ghrelin concentration is a variable that participates in weight control; however, the type of surgical approach is probably more related to weight loss in these patients.

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

Effect of Ghrelin on Memory Impairment in a Rat Model of Vascular Dementia

PURPOSE: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. METHODS: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 µg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. RESULTS: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. CONCLUSION: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

The Effect of Breastfeeding on Prevention of Maternal Hypertension: Systematic Review

PURPOSE: The purpose of this study is to clarify the relevance of breastfeeding and its preventive effect on maternal hypertension as well as to evaluate the theoretical mechanism behind of it through systematic evaluation of existing articles. METHODS: For systematic evaluation of literatures in recent 5 years, 5 most suitable articles were selected with the key words, (breastfeeding or breastfeed or lactation) AND (hypertension or high blood pressure or hypertensive disorders) from PubMed, EMBASE, and Cochran Library, and carefully reviewed by 2 researchers. RESULTS: Breastfeeding women have less frequently developed hypertension in their later life. Depending on the duration of breastfeeding, compared to nonbreastfeeding women, breastfeeding women's odds ratio for developing hypertension are 0.87 (95% confidence interval [CI], 0.76–0.99), 0.83 (95% CI, 0.68–1.00), and 0.79 (95% CI, 0.65–0.97) each for 0–6 months, 6–12 months, and greater than 12 months of breastfeeding. As the number of breastfeeding children increases, the incidence of maternal hypertension decreases. In addition, both partial and exclusive breastfeeding lower the risk of developing maternal hypertension. Though the mechanism of prophylactic effect of breastfeeding on hypertension is not conclusive, reset hypothesis, oxytocin release, the increase of ghrelin and protein peptide YY, as well as epigenetic programming are considered to be relevant to the etiology of the condition. CONCLUSION: Breastfeeding prevents maternal hypertension later in life. Studies show dose-response relationship of breastfeeding as the duration matters. In addition, both partial and exclusive breastfeeding have preventive effect on maternal hypertension. Numerous mechanisms are continuously being reported and further studies are needed for clarification.

Ghrelin improves the fine structure of atrial natriuretic factor (ANF) granules and intercalated disc junctions in experimentally-induced myocardial infarction in rats / La grelina mejora las estructuras finas de los gránulos de factor natriurético atrial (ANF) y las uniones intercaladas de disco en el infarto de miocardio inducido experimentalmente en ratas

Ghrelin is a novel growth hormone-releasing peptide administered to treat myocardial infarction (MI). However, the underlying mechanism of its protective effects against MI remains unclear. A total of sixty healthy Sprague Dawley male rats were included. The first one is the sham-operated control group were the rats that underwent the same surgical used to induce MI but without tying the left anterior descending coronary artery (LAD) and received normal saline (0.5 ml) as vehicle; the second MI model group were rats with LAD ligation and received normal saline (0. 5 ml) and the third one is MI+ghrelin group were rats that were exposed to surgery to induce MI but received ghrelin (100 µ/kg, orally, 2x/day). At the end of the experiment after 21 days post-MI, rats were sacrificed and processed for ultrastructural demonstration. Our experiment showed that ghrelin inhibited cardiomyocyte apoptosis. Concomitant administration of ghrelin with MI treated rats of this study appeared to show a considerable protection of the atrial tissues. This study revealed that the sarcoplasm was occupied by normal myofibrils with clear striations and others appeared with minor disruption. Normal distribution of atrionatriuretic factor (ANF) granules and well preserved mitochondrial integrity (preserved cristae, normal size and shape), nucleus chromatin arrangement and striated pattern of clear bands (Z and H) compared to the MI group. Intact intercalated disc with clear identification of fully formed fascia adherence and desmosomes with a reconstruction of gap junction (nexus) was also noticed. Atrial myocytes after myocardial infarction is often associated with subsequent heart failure, which could lead to a fatal outcome. In a rat model of experimental myocardial infarction, peripheral ghrelin administration attenuated myocyte dysfunction, well-preserved desmosome, adherent and gap junction of the intercalated disc and normally distributed ANF granules.

La grelina es un nuevo péptido liberador de hormona de crecimiento administrado para tratar el infarto de miocardio (IM). Sin embargo, el mecanismo subyacente de sus efectos protectores contra el IM aún no se conocen. Se incluyeron un total de 60 ratas macho Sprague Dawley saludables. En el grupo control se incluyeron ratas que fueron sometidas a una cirugía utilizada para inducir el IM, pero sin ligar la arteria coronaria descendente anterior izquierda (ACDAI) y recibieron suero fisiológico normal (0,5 ml) como vehículo; el segundo grupo modelo de IM fueron ratas con ligadura de ACDAI y recibieron suero fisiológico normal (0,5 ml); el tercer grupo estuvo formado por ratas con IM + grelina, expuestas a la cirugía para inducir IM pero luego recibieron grelina (100 m/kg, oralmente, 2x/día). Al final del experimento, 21 días después del infarto de miocardio, los animales fueron sacrificados y procesados para el estudio ultraestructural. Nuestro experimento mostró que la grelina inhibe la apoptosis de los cardiomiocitos. La administración concomitante de grelina en ratas con IM parece indicar una protección considerable de los tejidos atriales. Además, el estudio reveló que el sarcoplasma estaba ocupado por miofibrillas normales con estriaciones claras y otras con una alteración menor. Se encontró una distribución normal de los gránulos del factor natriurético atrial (FNA) e integridad mitocondrial bien conservada (crestas conservadas, tamaño y forma normales), disposición de la cromatina del núcleo y patrón estriado de bandas claras (Z y H) en comparación con el grupo IM. También se observó un disco intercalado intacto con una clara identificación de la adherencia de la fascia completamente formada y desmosomas con una reconstrucción de la unión gap (nexo). Los miocitos atriales, después de un infarto de miocardio, a menudo se asocian con insuficiencia cardíaca posterior, que podría conducir a un desenlace fatal. En un modelo de rata de infarto de miocardio experimental, la administración de grelina periférica atenuó la disfunción de miocitos, con conservación del desmosoma, adherencia y unión de la brecha del disco intercalado y una distribución normal de los los gránulos de FNA.

Evaluating the Levels of Nesfatin-1 and Ghrelin Hormones in Patients with Moderate and Severe Major Depressive Disorders

OBJECTIVE: The goal of this study was to evaluate the importance of nesfatin-1, acylated and des-acylated ghrelin, which are known as energy regulatory hormones, in patients with moderate and severe major depression disorders (MDD). METHODS: Thirty patients with a moderate degree of MDD and, 30 with a severe degree of MDD were used as participants in this study. Thirty subjects without depression were enrolled as a control group. The Hamilton Depression Rating Scale was used to classify the patients with MDD. Blood samples were taken after overnight fasting. The plasma nesfatin-1, acylated ghrelin and des-acylated ghrelin levels were measured using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: The nesfatin-1, the acylated ghrelin and the des-acylated ghrelin levels were found to be significantly higher in severe MDD (3.92±0.4 ng/mL; 88.56±4.1 pg/mL; 962.76±67 pg/mL) as compared to moderate MDD (2.91±0.5 ng/mL; 77.63±4.19 pg/mL; 631.16±35 pg/mL), or the control (1.01±0.3 ng/mL; 58.60±9.00 pg/mL; 543.13±62 pg/mL), respectively. CONCLUSION: Although nesfatin-1 and ghrelin are known as adversely affecting the hormones involving the regulation of appetite and food intake, they all increase in depressive patients and are even associated with the severity of the disease. In clinical medicine, the evaluation of the role of nesfatin-1 and ghrelin in endocrine and neu-roendocrine regulation of major metabolic functions is an important key mechanism in solving numerous diseases associated with endocrine and neuroendocrine disturbance. Increased levels of nesfatin-1 and ghrelin may also be important criteria in describing the prognoses of the patients and the effectiveness of the treatments.

Different Endocrine Effects of an Evening Dose of Amitriptyline, Escitalopram, and Placebo in Healthy Participants

OBJECTIVE: The primary aim of this study was to further characterize the acute effects of amitriptyline (AMI) and escitalopram (ESC) on serum levels of ghrelin, leptin, cortisol and prolactin in healthy humans. METHODS: Eleven healthy male participants received a single dose of AMI 75 mg, ESC 10 mg, or placebo (PLA) at 9:00 PM in a double blind, randomized, controlled, repeated measures study separated by one week. Fasting morning serum levels (7:00 AM) of ghrelin, leptin, cortisol and prolactin were assessed. RESULTS: A repeated measures multivariate analysis of variance revealed a significant main effect for the factor condition (AMI, ESC, PLA). Subsequent univariate analyses demonstrated significant condition effects for ghrelin and cortisol. Post-hoc analyses demonstrated a significant reduction of ghrelin levels after AMI in comparison to PLA, and a significant reduction of cortisol levels after AMI in comparison to both ESC and PLA. Other contrasts did not reach statistical significance. CONCLUSION: Administration of a single dose of AMI, but not of ESC, leads to a significant reduction in morning serum ghrelin and cortisol levels. No effects on leptin and prolactin levels were observed. The differential impact of AMI and ESC on hormones might contribute to different adverse effect profiles of both substances.

TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.