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Objectives: The pandemic of coronavirus disease 2019 (COVID-19) has been one of the major health concerns for all the countries around the globe. This study was aimed to study the potential effect of COVID-19 virus on the level of blood ghrelin appetite hormone in order to determine the influence of this infection on the patient appetite. Methods: This is a cross-sectional study was conducted between July and the end of August 2020 in the western region of Saudi Arabia. A total of 50 confirmed positive patients with COVID-19 (positive group) and 30 control healthy subjects with negative blood samples (negative group) were collected to determine the level of ghrelin appetite hormone using the human ghrelin (GHRL) ELISA technique. A student’s t-test was carried out to find out the statistical change between different study groups. Results: The serum total ghrelin concentrations, on average, were 51.32 pg/mL on positive group and 50.37 pg/mL on negative group, respectively. The difference of ghrelin was statistically insignificant between the two groups (P >0.05). Although the sample size of the study was small, the results showed high number of COVID-19 cases in male than female. Conclusion: The current data shows that there are no significant changes in the level of serum ghrelin hormone in COVID-19 patients. Consequently, it might be possible that the ghrelin hormone showed potential changes in the saliva compared to the effect in the blood. Thus, a further analysis of the ghrelin hormone in the saliva of COVID-19 patients will be conducted in the near future.

Objective Atrophic gastritis may affect circulating ghrelin levels and, indirectly, body mass index. The aim of this study was to investigate the relationship between atrophic gastritis, focusing on autoimmune atrophic gastritis and advanced stages of atrophic gastritis, serum ghrelin levels and BMI. Methods Sixty-three patients, of whom 18 had autoimmune atrophic gastritis, 27 non-autoimmune antrum and corpus atrophic gastritis, and 18 non-atrophic gastritis or antrum-limited atrophic gastritis (control group) were assessed. All participants underwent endoscopy with multiple gastric biopsies. Atrophic gastritis was diagnosed by histology, classified according to the Updated Sydney System and staged by the Operative Link on Gastritis Assessment (OLGA) Classification. Total serum ghrelin, body weight and height were measured. Results Compared with control patients (144.6 ± 111 pg/ml), mean serum level of total ghrelin was higher in patients with autoimmune atrophic gastritis (226.08 ± 243.03 pg/ml, P = 0.65) and lower in those with both antrum and corpus atrophic gastritis (74.51 ± 37.38 pg/ml, P = 0.12), although differences were not statistically significant. Serum ghrelin decreased in patients with advanced OLGA stages of atrophic gastritis. In non-obese patients BMI was significantly lower in those with both antrum and corpus atrophic gastritis than in control patients (23.1 ± 1.8 vs. 24.5 ± 1.6, P = 0.01), also after adjustment for age and sex (P = 0.02); BMI was positively correlated with serum total ghrelin (r = 0.51, P < 0.001). Conclusion Advanced stages of atrophic gastritis, but not autoimmune atrophic gastritis, seem to be associated with lower serum levels of ghrelin and lower BMI. In non-obese patients, BMI was positively correlated with total serum ghrelin.

This research paper addresses the hypothesis that intensive cooling management during the summer improves the secretion of metabolic hormones in dairy cows. To test this hypothesis, we characterized the effect of different cooling managements on the different ghrelin isoforms and leptin secretion of 20 Israeli-Holstein dairy cows during 5 weeks during heat stress. The cows were divided into two groups: one was exposed to 5 cooling sessions per day (5 CS) and the other to 8 cooling sessions per day (8 CS). Blood was collected and leptin and ghrelin isoforms level were radioimmunoassayed. Analysis of the interaction between coolings and the week of the experiment showed that the 8 CS group consumed more food and produced more milk, although neither difference was statistically significant. In addition, the 8 CS group exhibited higher blood levels of acyl-ghrelin and leptin as compared to the 5 CS group. Conversely, the blood levels of total ghrelin were lower in the cows exposed to 8 CS as compared to cows from the 5 CS treatment. Furthermore, a significant correlation was found only between total ghrelin levels and the weeks, but not with other parameters examined. We further compared digestibility as well as stress parameters between the groups. We found that the 8 CS group cows ruminated and lay down more hours during a day and simultaneously had better activity time. No significant difference was detected between groups in milk yield and digestibility parameters. Our results suggest that intensive cooling management during the hot season influences the levels of metabolic hormones in the circulation and helps to mitigate the detrimental effect of heat stress on dairy cow welfare and production.

Salivary hormone analysis is a non-invasive alternative to blood-borne hormone analysis. The orexigenic hormone ghrelin has been detected in human saliva, though the relationship between salivary and blood-borne ghrelin and salivary ghrelin's association with energy intake (EI) and appetite remains unclear. The primary aim of this study was to compare salivary and plasma ghrelin responses to dairy breakfast drinks varying in protein content and quantity, and to determine the relationship between salivary ghrelin and EI and appetite. Participants (n = 25) consumed four test drinks, varying in protein content and quantity, on four separate days in a double-blind randomized controlled study. Salivary and plasma total ghrelin were measured at 0, 30, 60 and 120 min and appetite perceptions at 0, 30, 60, 90 and 120 min. A buffet-style test meal was presented at 120 min to measure ad libitum EI. There was no correlation between the sample means for fasted salivary and plasma ghrelin (r = 0.099, p = 0.637). Furthermore, there was no within-participant association between fasted salivary and plasma ghrelin (r = -0.041, p = 0.725). Mean bias between fasted salivary and plasma ghrelin was -448 pg/ml (95% confidence intervals (CI) = -623 - -273 pg/ml) and upper and lower limits of agreement (LOA) were 427 pg/ml and -1324 pg/ml, respectively. Variation in postprandial levels of salivary and plasma ghrelin within-participants were not associated (r = -0.004, p = 0.943). There was no significant association between EI and salivary (r = 0.003, p = 0.979) or plasma (r = -0.080, p = 0.492) ghrelin. Salivary ghrelin was not significantly correlated with composite appetite score (r = 0.023; p = 0.654), though plasma ghrelin was (r = 0.225, p 0.001). Mean bias between postprandial salivary and plasma ghrelin was -210 pg/ml (95% CI = -380 - -40 pg/ml) and upper and lower LOA were 641 pg/ml and -1061 pg/ml, respectively. These findings suggest that salivary and plasma ghrelin responses to drinks varying in protein content and quantity are unrelated and that salivary ghrelin is not associated with EI or appetite perceptions in healthy non-obese adults. This trial was registered at www.clinicaltrial.gov (NCT01597024).

Background Ghrelin plays significant roles in regulating appetite, food intake, and metabolism. Furthermore, the ghrelin system is increasingly being studied in relation to alcohol seeking behaviors. To this end, it is important to understand the possible effects of alcohol intake on the ghrelin system. The aim of the present study was to investigate the association between alcohol drinking and circulating ghrelin levels in a large sample of cigarette-smoking, non-alcohol-dependent male individuals. Methods We utilized data from two nested case-control studies (study A, n = 807; study B, n = 976) based within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial. Data on alcohol consumption (grams of pure alcohol consumed per day) were obtained via a food frequency questionnaire. Blood samples were also collected (after 12 h of fasting), and serum concentrations of total ghrelin were measured by radioimmunoassay. Results Dichotomous comparison between alcohol drinkers (>0 g/day of alcohol intake) and non-drinkers (0 g/day of alcohol intake) found higher total ghrelin levels among individuals who drank alcohol than those who did not, with statistically significant results in study A [F (1, 798) = 4.32, P = 0.03] and less robust results in study B [F (1, 966) = 2.62, P = 0.10], controlling for a list of factors that may influence ghrelin levels and/or differ between drinkers and non-drinkers. Bivariate correlational analysis among drinkers found no association between the quantity of daily alcohol intake and blood total ghrelin concentrations. Conclusion These results indicate elevated ghrelin levels among alcohol drinkers and provide additional/relevant information on the complex interaction between alcohol use and the ghrelin system.

Sex hormones are suggested to influence energy intake (EI) and metabolic hormones. This study investigated the influence of menstrual cycle (MC) and hormonal contraceptive (HC) cycle phases on EI, energy availability (EA), and metabolic hormones in recreational athletes (eumenorrheic, NHC = 15 and monophasic HC-users, CHC = 9). In addition, 72-h dietary and training logs were collected in addition to blood samples, which were analyzed for 17β-estradiol (E2), progesterone (P4), leptin, total ghrelin, insulin, and tri-iodothyronine (T3). Measurements were completed at four time-points (phases): Bleeding, mid-follicular (FP)/active 1, ovulation (OVU)/active 2, mid-luteal (LP)/inactive in NHC/CHC, respectively. As expected, E2 and P4 fluctuated significantly in NHC (p &lt, 0.05) and remained stable in CHC. In NHC, leptin increased significantly between bleeding and ovulation (p = 0.030) as well as between FP and OVU (p = 0.022). No group differences in other measured hormones were observed across the MC and HC cycle. The mean EI and EA were similar between phases, with no significant differences observed in macronutrient intake over either the MC or HC. While the MC phase might have a small, but statistically significant effect on leptin, the findings of the present study suggest that the MC or HC phase does not significantly alter ad libitum EI or EA in recreational athletes.

BackgroundThe present study aimed to investigate the association between estradiol, acylated, des-acylated, total ghrelin levels along with pathological parameters and epithelial ovarian cancer (EOC) odds in postmenopausal women.MethodsA case-control study was carried out on 45 EOC patients and 33 age-matched postmenopausal women as the control group. Plasma levels of estradiol, acylated, des-acylated, and total ghrelin were measured by ELISA method.ResultsEstradiol’s plasma levels were significantly higher in EOC patients compared to control women (P < 0.001). Although acylated, des-acylated, and total ghrelin levels were not associated with EOC in logistic regression models, estradiol levels were significantly related to the increase in EOC odds (OR: 1.083, 95% CI: 1.037-1.13, P < 0.001). However, estradiol levels in the two first quartiles (Q1, Q2) were associated with decreased odds of EOC (OR: 0.011, 95% CI: 0.001-0.118, P < 0.001, and OR: 0.030, 95% CI: 0.003-0.284, P = 0.002, respectively). For those patients in the third quartile of plasma des-acylated and total ghrelin compared to those in the highest (Q4), the multivariate odds ratios of EOC were respectively 0.192 and 0.25.ConclusionsIn conclusion, higher concentrations of des-acylated and total ghrelin might be associated with the decreased EOC odds. Furthermore, the findings suggest that high levels of estradiol might be a potential odds factor in EOC, however, lower estradiol levels may have a protective effect on EOC development.

The aims of this study were: to compare total ghrelin concentration throughout pregnancy between lactating cows and heifers, and to study the response to acute feed restriction in pregnant or non-pregnant heifers. Blood samples were collected each month of pregnancy from cows (n = 5) and heifers (n = 5) and analyzed for total ghrelin concentration. Compared to pre-conception values, ghrelin concentrations tended to be greater during 3rd month of pregnancy in heifers, whereas they were higher in the 7th, 8th and 9th months in lactating cows, but no difference was detected between lactating cows and heifers. In experiment two, pregnant (n = 4) and non-pregnant (n = 4) heifers were fasted for 24 h. Blood samples were collected 0, 4, 8, 12, 16 and 24 h of fasting and were assayed for, insulin, glucose, cortisol, BHBA and NEFA concentrations, and at time points 0, 8, 16 and 24 for total ghrelin determination. Compared to satiety, ghrelin concentrations were higher at 8th, 16th and 24th hour of fasting in pregnant and at 8th hour in non-pregnant animals, but no difference was detected between pregnant and non-pregnant heifers. Pregnant heifers had lower glucose concentrations than non-pregnant ones. Insulin concentrations were reduced at 4 and 8 h of fasting in pregnant heifers, and stayed unaffected in non-pregnant ones. Cortisol concentrations increased after 4th hour and remained elevated throughout the sampling period in pregnant heifers, while they increased at 24th h in non-pregnant animals. Here, we provide evidence that total ghrelin concentrations rise in response to feed restriction. Albeit no group effect was evident, our results imply that a) during the last trimester of pregnancy total ghrelin is secreted in different pattern between lactating cows and heifers, b) pregnant animals are more responsive than non-pregnant ones to hunger induced stress.

OBJECTIVE: Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. AIM OF THE STUDY: To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. METHODS: Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). RESULTS: Compared with males, females had higher (p

Background : Desacyl ghrelin is acylated by ghrelin O-acyltransferase (GOAT) and converted to acyl ghrelin. To date, little is known about the relationship among the levels of these two forms of ghrelin, GOAT level, and insulin resistance in Asian individuals. The purpose of this study was to determine the relationship between insulin resistance and the levels of plasma acyl ghrelin, desacyl ghrelin, and GOAT in asymptomatic middle-aged Korean men. Methods : This cross-sectional study evaluated 78 asymptomatic middle-aged Korean men with metabolic syndrome (MS). We examined the correlation between the plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT and sociodemographic, dietary, anthropometric, and metabolic parameters, as well as the association between insulin resistance and plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT. Results : The levels of desacyl ghrelin and total ghrelin were significantly lower in the MS group than in the non-MS group (P

espanolObjetivo: evaluar la relacion entre la concentracion de suero y la leche materna y la concentracion de grelina y leptina en leche materna en madres lactantes segun el tipo de alimentacion. Metodos: diseno de cohorte realizado en 131 diadas madre-lactante que ingresaron en una sala de puerperio fisiologico. Variables independientes: tipo de alimentacion, lactancia materna completa (LMC, 56,5%) y lactancia materna parcial (LMP, 43,5%). Variables dependientes: concentracion serica de grelina total (pg/ml) y leptina (ng/ml), leche humana pre-tetada y pos-tetada a las ocho y 16 semanas. Se utilizaron pruebas no pareadas t de Student, U de Mann-Whitney, correlacion de Pearson, coeficiente de determinacion y regresion linear. Resultados: la concentracion de grelina y leptina en leche humana pre-tetada fue mayor que en leche humana pos-tetada en ambos grupos a las ocho y 16 semanas. La concentracion de grelina y leptina fue mayor en suero que en leche humana en ambos grupos; estos valores mostraron una correlacion lineal directa y significativa con la excepcion de la grelina en el grupo de LMC. La concentracion serica de leptina en las madres explico el 32% de la varianza de su concentracion en leche humana en LMC y el 13% en madres en LMP. Conclusion: el gradiente de leche humana pre-tetada/pos-tetada sugiere un mecanismo de regulacion e ingestion de leche. La concentracion de grelina y leptina fue mayor en suero que en leche humana y los coeficientes de determinacion sugieren una transferencia de suero-leche, ademas de una regulacion de la sintesis por la glandula mamaria, el tejido adiposo u otros organos. EnglishObjective: we assessed the relationship between serum and human foremilk and hindmilk concentrations of ghrelin and leptin in nursing mothers according to the type of feeding. Methods: this cohort design was carried out on 131 mother-newborn dyads admitted to a physiological puerperium ward. The independent variables were the type of feeding, full breastfeeding (FBF, 56.5%) and partial breastfeeding (PBF, 43.5%). The dependent variables were the concentration of total ghrelin (pg/ml) and leptin (ng/ml) in serum, foremilk and hindmilk at eight and 16 weeks. Fasting blood samples were obtained from the nursing mothers at four months for serum assays. Unpaired Student’s t-test, Mann-Whitney U test, Pearson’s correlation tests, coefficient of determination and linear regression were used. Results: the concentration of ghrelin and leptin in hindmilk was higher than that of foremilk in both groups at eight and 16 weeks. The concentration of ghrelin and leptin was higher in serum than in foremilk in both groups. These values showed a direct and significant linear correlation with the exception of ghrelin in the FBF group. The serum concentration of leptin in mothers explained 32% of the variance of its concentration in foremilk in the FBF and 13% in the PBF groups. Conclusion: the hindmilk/foremilk gradient suggests an intake regulating mechanism during the fed. The concentration of ghrelin and leptin was higher in the serum than in foremilk and its correlation and determination coefficients could suggest plasma-milk transfer in addition to synthesis regulation by the mammary gland, adipose tissue or other organs.

In two experiments, we studied (a) the changes of LH secretion in heifers under different feeding schedules and (b) total ghrelin concentration at oestrus in cows and heifers. In experiment one, synchronized heifers were allocated in three groups (R, regularly fed controls; F, fasted; and F-F fasted-fed). One day after the completion of the oestrous induction protocol, group F and F-F animals stayed without feed for 24 hr; thereafter, feed was provided to R and F-F cattle; 2 hr later, GnRH was administered to all animals. Blood samples were collected for ghrelin, progesterone, LH and cortisol concentrations. Fasting caused increased ghrelin concentrations in groups F and F-F, while in response to GnRH, LH surge was significantly attenuated in groups F and F-F compared to R. In experiment 2, lactating cows and heifers were used. On day 9 of a synchronized cycle, PGF2α was administered, and blood samples were collected twice daily until the third day after oestrus and analysed for progesterone, estradiol, ghrelin, glucose and BHBA concentrations. No difference was recorded between groups in steroids and BHBA concentrations. In comparison to mid-luteal values, ghrelin concentrations significantly increased at perioestrual period in cows, but not in heifers. This study provides evidence that starving-induced elevated ghrelin concentrations can have suppressing effect on LH secretion, even after ghrelin's restoration to basal values and that during oestrus, ghrelin secretion is differently regulated in cows and heifers, likely being independent from oestradiol concentrations. Further research is required to identify the determining factors that drive the different regulation of ghrelin secretion in cows and heifers.

An electrochemical immunosensor for ghrelin (GHRL) determination in saliva is reported. Anti-GHRL was immobilized onto Protein G-magnetic beads and a competitive immunoassay involving biotinylated GHRL and alkaline phosphatase-streptavidin was implemented. Once conjugate was magnetically captured on a screen-printed carbon electrode, GHRL quantization was accomplished by DPV of 1-naphtol formed upon addition of 1-naphtyl phosphate. A linear range between 10−3 and 103 ng/mL GHRL, and a LOD of 7 pg/mL, much smaller than those from commercial ELISA kits, were found. The usefulness of the immunosensor was demonstrated by analyzing human saliva spiked with GHRL at 0.01, 0.1, 1 and 10 ng/mL.

Objective: This study aimed to investigate how central obesity and hypertension modulate unacylated ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and the ratios of UnAG/obestatin, AG/obestatin, and total ghrelin/obestatin. Methods: Circulatory abundances of UnAG, AG, obestatin and GH were determined in 387 Hong Kong Chinese female adults with age between 24 to 86 years based on a 2 × 2 factorial design of hypertension (blood pressure ≥140/90 mmHg) and central obesity (waist circumference or WC ≥80 cm). Participants were categorized as neither hypertensive nor centrally obese (NHNO; n = 105), hypertensive but not centrally obese (HNO; n = 102), centrally obese but not hypertensive (NHO; n = 74) and hypertensive and centrally obese (NO; n = 106). Pearson's correlation analyses were performed to detect the association between the peptides examined with WC and blood pressure. The main and interaction effects of hypertension and central obesity were examined by generalized estimating equations analyses. Results: Correlation analyses revealed that systolic blood pressure was negatively correlated with AG/obestatin, UnAG/obestatin and total ghrelin/obestatin ratios, AG, total ghrelin, and GH, while diastolic blood pressure was negatively correlated with UnAG/obestatin, total ghrelin/obestatin ratios, and GH. WC was negatively correlated with AG/obestatin, UnAG/obestatin, and total ghrelin/obestatin ratios, UnAG, AG, total ghrelin, GH, and obestatin. Interaction effects of hypertension and central obesity were observed on UnAG/obestatin, AG/obestatin and total ghrelin/obestatin ratios, and obestatin. Obestatin in NHO group was significantly higher compared to NHNO and HO groups. UnAG/obestatin, AG/obestatin, and total ghrelin/obestatin ratios were higher in NHNO group compared to HNO and HO groups. Main effects of central obesity and hypertension were observed in UnAG, total ghrelin and GH. The HO group manifested the lowest level of UnAG, total ghrelin and GH among all the groups studied. Main effect of hypertension was observed on AG, suggesting that hypertensive individuals exhibited lower levels of AG regardless of central obesity. Conclusion: Circulatory ghrelin gene products and GH exhibit different modes of modulation in response to the co-manifestation of multiple cardiovascular risk factors compared with a single risk factor alone.

We assessed the plasma acyl ghrelin (AG), unacyl ghrelin (UAG), and total ghrelin (TGhr) levels in Chinese adults with pre-diabetes and newly diagnosed diabetes mellitus (NDDM) after an oral glucose tolerance test (OGTT), and abdominal subcutaneous fat area and visceral fat area (VFA) were measured. Fasting AG level was increased in the impaired fasting glucose (IFG) combined with impaired glucose tolerance (IFG+IGT) and NDDM groups. AG, UAG, and TGhr levels were significantly decreased post-OGTT, and the decrements of 30-min AG, UAG, and TGhr post-OGTT were not significantly different among groups. UAG and TGhr levels did not differ significantly among the normal glucose tolerance (NGT), IFG and NDDM groups, but they decreased obviously in the IFG+IGT and impaired glucose tolerance (IGT) groups. The NDDM group had larger VFA than the NGT, IGT, and IFG+IGT groups, even after adjustment for height, it was still larger than the NGT group. The factors such as dyslipidemia and obesity which are prone to develop insulin resistance (IR) and decrease insulin sensitivity (IS) were negatively correlated with UAG and TGhr, positively with AG/UAG, while no correlations with AG. In terms of evaluating IS and IR, AG/UAG ratio may be superior in AG concentration. Our findings suggest that relative sufficiency of AG, the deficiency of TGhr and UAG are already present in IFG+IGT patients. We speculate that there is UAG resistance in severe hyperglycemia (diabetic state), which could produce elevated TGhr and UAG compared to IFG+IGT group. In the development of T2D, increase of VFA could be the initiating factor, leading elevated AG, reduced UAG, IR, decreased IS, and finally hyperglycemia.

Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence.We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included.Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.

Eccentric exercise has been suggested to improve muscle atrophy, muscle function, and insulin sensitivity. The aim of this study was to examine the effect of acute eccentric exercise on appetite-related hormones, food preferences, and food intake. Fourteen moderately active men were recruited to participate in this study (age 24.2 ± 5.5 years; BMI 23.4 ± 3.3 kg/m2; VO2max 48.9 ± 3.1 ml/kg/min). Three different conditions were implemented; no exercise, flat running “inclination 0” and downhill running “inclination –12%.” Appetite-related hormones, subjective appetite sensations, food preference and reward, and ad libitum food intake were measured at pre-, immediately post-, and 24 h post exercise. There were no significant median changes in total ghrelin or pancreatic peptide concentrations between conditions. There were also no median differences in subjective appetite ratings or energy intake between conditions, but the median change in explicit liking of sweet versus savory foods differed significantly between pre-exercise and 24 h post exercise ( p = .013). Post-hoc analysis observed a significant difference in the pre-exercise to 24 h post exercise change between front running and downhill running ( p = .023), and indicated greater liking of savory foods over sweet foods in downhill running than front running. However, no further differences were seen between conditions for the remaining food preference parameters, suggesting there were no systematic trends in these data. In conclusion, there was no effect of front and downhill running on eating behavior as compared to a nonexercise control condition, but these data need to be replicated in a larger and more heterogeneous sample.

Reducing dietary energy density (ED) promotes weight loss; however, underlying mechanisms are not well understood. The purpose of this study was to determine if low-ED diets facilitate weight loss through actions on ghrelin and peptide YY (PYY), independent of influences of psychosocial measures. Seventy-one obese women (BMI 30-40 kg/m(2)) ages 22-60 years received counseling to reduce ED. Fasting blood samples were analyzed for total ghrelin and total PYY by radioimmunoassay at months 0, 3, 6, and 12. Restraint, disinhibition, and hunger were assessed by the Eating Inventory. Body weight (-7.8 ± 0.5 kg), BMI (-2.9 ± 0.2 kg/m(2)), body fat (-3.0 ± 0.3%), and ED (-0.47 ± 0.05 kcal/g or -1.97 ± 0.21 kJ/g) decreased from months 0 to 6 (p

Peptide YY (PYY) and ghrelin exhibit a reciprocal association and antagonistic physiological effects in the peripheral circulation. Research has yet to clarify the effect of weight loss on the 24h profile of PYY or its association to 24h ghrelin. We sought to determine if diet- and exercise-induced weight loss affects the 24h profile of PYY and its association with 24h ghrelin in normal weight, premenopausal women. Participants (n = 13) were assessed at baseline (BL) and after a 3-month diet and exercise intervention (post). Blood samples obtained q10 min for 24h were assayed for total PYY and total ghrelin q60 min from 0800 to 1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. The ghrelin/PYY ratio was used as an index of hormonal exposure. Statistical analyses included paired t-tests and linear mixed effects modeling. Body weight (-1.85 ± 0.67 kg; p = 0.02), and body fat (-2.53 ± 0.83%; p = 0.01) decreased from BL to post. Ghrelin AUC (5252 ± 2177 pg/ml/24h; p=0.03), 24h mean (216 ± 90 pg/ml; p = 0.03) and peak (300 ± 134 pg/ml; p = 0.047) increased from BL to post. No change occurred in PYY AUC (88.2 ± 163.7 pg/ml; p = 0.60), 24h mean (4.8 ± 6.9 pg/ml; p = 0.50) or peak (3.6 ± 6.4 pg/ml; p = 0.58). The 24h association between PYY and ghrelin at baseline (p = 0.04) was weakened at post (p = 0.14); however, the ghrelin/PYY lunch ratio increased (p = 0.01) indicating the potential for ghrelin predominance over PYY in the circulation. PYY and ghrelin are reciprocally associated during a period of weight stability, but not following weight loss. An "uncoupling" may have occurred, particularly at lunch, due to factors that modulate ghrelin in response to weight loss.

The aim of the study was to assess the impact of varying intensity of exercise on ghrelin levels in half-blood jumping horses during training season. Blood samples were collected in the period of intense and moderate exercise. Serum concentrations of active and total ghrelin were measured using commercial RIA kits. Exercise did not cause the disruption in energy homeostasis, which was confirmed by the conducted tests. Total concentration of ghrelin measured during the increased effort intensity elevated in stallions (from 1031.45 to 1732.19 pg/mL at P ≤ 0.05). The opposite situation occurred in the case of active ghrelin, which concentration did not increase significantly in mares (from 26.21 to 28.46 pg/mL), whereas an insignificant decrease was noted in stallions (from 24.19 to 22.54 pg/mL). The only significant difference between stallions and mares was noted in the 2nd sampling (P = 0.015). The research proved that the fluctuations of both studied parameters did not reflect a negative impact of the increased effort.

There is a hypothesis that ghrelin could take part in the central effects of alcohol as well as function as a peripheral indicator of the changes which occur during long-term alcohol consumption. The aim of this study was to determine a correlation between alcohol concentration and acylated and total form of ghrelin after a single administration of alcohol (intraperitoneal, i.p.) (experiment 1) and prolonged ethanol consumption (experiment 2). The study was performed using Wistar alcohol preferring (PR) and non-preferring (NP) rats and rats from inbred line (Warsaw High Preferring, WHP; Warsaw Low Preferring, WLP). It was found that ghrelin in ethanol-naive WHP animals showed a significantly lower level when compared with the ethanol-naive WLP or Wistar rats. After acute ethanol administration in doses of 1.0; 2.0 and 4.0 g/kg, i.p., the simple (WHP) or inverse (WLP and Wistar) relationship between alcohol concentration and both form of ghrelin levels in plasma were found. Chronic alcohol intake in all groups of rats led to decrease of acylated ghrelin concentration. PR and WHP rats, after chronic alcohol drinking, had lower levels of both form of ghrelin in comparison with NP and WLP rats, respectively, and the observed differences in ghrelin levels were in inverse relationship with their alcohol intake. In conclusion, it is suggested that there is a strong relationship between alcohol administration or intake, ethanol concentration in blood and both active and total ghrelin level in the experimental animals, and that ghrelin plasma concentration can be a marker of alcohol drinking predisposition.

Ghrelin and adiponectin have been found in breast milk and are considered to take part in the regulation of growth and energy metabolism of infants. Our aims were to determine ghrelin and adiponectin levels in breast milk and serum samples of mothers and their infants, and to investigate the relationship between their levels and anthropometry of newborn infants during early postnatal life. Total and active ghrelin and adiponectin levels were studied in breast milk, and the serum samples of 25 healthy lactating women and their healthy fullterm infants were taken at the 1st and 4th months of life. Anthropometric measurements of infants were also performed during the study period. Breast milk and infant serum active ghrelin levels were found to be significantly increased at the 4th month of life compared with 1st month levels (p < 0.05). Maternal serum total ghrelin and infant serum adiponectin levels were found to be significantly reduced at the 4th month of life (p < 0.05). Breast milk active ghrelin levels were higher than the infant and maternal serum active ghrelin at the 1st and 4th months (p < 0.05). There was a negative significant correlation between the level of infant serum active ghrelin levels and BMI of infants at the 1st month. A positive significant correlation was found between the level of 1st month infant serum adiponectin levels and weight gain of infants during the study period. Fourth month infant serum adiponectin were also positively correlated with weight and BMI of infants at the 4th month and the weight gain during study period. There was a positive significant correlation between the level of 4th month breast milk active ghrelin and weight gain of infants during the study period. Ghrelin and adiponectin are involved in postnatal growth of infants. Ghrelin in breast milk also seems to be related to the growth of infants during early postnatal life. The sources of these peptides in breast milk are probably both maternal serum and breast tissue itself.

In hemodialysis (HD) patients studies have shown that plasma ghrelin is increased and it has been speculated that ghrelin levels might be related to systemic inflammation. The present study attempted to correlate the serum levels of total ghrelin with serum TNF-α and IL-6, and with nutritional status and body composition in HD patients. Forty-seven HD patients from a single dialysis unit (18 women, mean age 55.3±12.2 yr; BMI 24.4±4.2kg/m(2); % body fat 29.4±7.4%) were studied and compared to 21 healthy subjects (12 women, 50.7±15.7 yr and BMI 25.6±4.0kg/m(2); % body fat 30.0±5.7%). Biochemical data, serum total ghrelin, TNF-α and IL-6 levels were measured. The body composition was evaluated by dual energy X-ray absortiometry (DEXA) and energy and protein intake were evaluated. Patients showed elevated plasma ghrelin levels when compared to healthy subjects (1.14±1.0ng/mL vs 0.58±0.4; p0.001). There was a positive correlation between ghrelin levels and TNF-α (r=0.25; p0.04), IL-6 (r=0.42; p0.02), and a negative correlation between TNF-α and protein intake (r=-0.28; p0.03), and energy intake (r=-0.34; p0.01). No correlation was observed with any aspect of body composition. Plasma ghrelin levels are elevated in HD patients and associated with the state of systemic inflammation. We suggest that the inflammatory state may affect ghrelin bioactivity and metabolism in hemodialysis patients.

The aim of this study was to validate two commercially available ELISA assays for total ghrelin measurement in dogs: one canine-specific and one originally designed for measuring human ghrelin. The two assays showed intra-assay coefficient of variations (CVs) lower than 10%, while the inter-assay CVs exceeded the 15% limit. Sample dilutions resulted in linear regression equations with correlation coefficients close to 1. In order to compare methods and verify ability of the ghrelin assays to differentiate between low and high levels, ghrelin concentrations were measured in plasma samples obtained before and at different times after glucose administration in five Beagle dogs. A statistically significant changes in ghrelin after glucose administration was recorded only with assay B. In conclusion, the human ELISA validated in this study showed a good intra-assay precision, accuracy, and when applied to the glucose injection study, was better in distinguishing high and low canine ghrelin levels than the canine ELISA assay.

Background: Ghrelin and adiponectin, which are considered to take part in the regulation of energy metabolism, have been found in breast milk and cord blood. The aims of this study were to determine ghrelin and adiponectin levels in colostrum, cord blood and maternal serum and to investigate the correlations between colostrum and cord blood levels of these peptides and the anthropometry of newborn infants and their mothers. Methods: Total ghrelin (TGHR), free ghrelin (FGHR) and adiponectin levels were studied in colostrum and the serum samples of 25 healthy lactating women and the cord blood of their healthy full-term infants. Results: No significant differences could be found among TGHR and adiponectin levels in colostrum, cord blood and maternal serum. The median FGHR level in colostrum was significantly higher than that of maternal serum and cord blood. The colostrum TGHR was negatively correlated with body mass index (BMI) and weight of the infants at birth. TGHR and FGHR levels in colostrum were found to be positively correlated with those of maternal TGHR and FGHR concentrations, respectively. Adiponectin levels in colostrum were not correlated with BMI or birthweight of the infants or BMI of the mothers. Conclusion: These findings suggest that the source of ghrelin in breast milk is probably both breast tissue itself and the serum of the mother. Ghrelin in colostrum seems to be related to the anthropometry of infants even at birth, unlike adiponectin.

Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UG) forms, and higher plasma total ghrelin (TG) and UG may be cross-sectionally associated with lower insulin resistance in metabolic syndrome patients. The potential value of ghrelin forms in predicting insulin resistance and its time-related changes in community-based population cohorts remains unknown.We measured TG, AG and calculated UG (TG-AG) in 716 individuals from the North-East-Italy MoMa study (age: 55 ± 9 years, BMI: 29 ± 5 kg/m(2), M/F:349/367) to test the hypothesis that circulating TG and UG, but not AG are negatively associated with insulin resistance (HOMA). We further hypothesized that baseline TG and UG negatively predict 5-year HOMA changes in a 350-individual subgroup.Baseline TG and UG were associated negatively with HOMA after adjusting for gender and body mass index (BMI). Baseline gender- and BMI-adjusted TG and UG were also negatively associated with HOMA at 5-year follow-up (n = 350), and changes in TG and UG were negatively associated with changes in HOMA (P 0.05) after adjustment for anthropometric and metabolic confounders. No statistically significant correlations were observed between AG and baseline or 5-year HOMA.In a North-East Italy community-based population cohort, plasma TG and UG but not AG are negatively associated with HOMA. TG and UG and their changes also independently predict 5-year HOMA changes. TG and UG are therefore novel potential modulators of insulin resistance and may contribute to predict its time-related changes in humans.

To explore the hypothesis that high ghrelin levels contribute to obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels observed in older persons with PWS exist in very young children, before the onset of hyperphagia.We measured ghrelin levels in nine children with PWS (17-60 months of age) and eight healthy control subjects of equivalent body mass index (BMI), age, and sex.PWS and control groups had equivalent BMI (16.8 +/- 1.4 vs 16.1 +/- 0.9 kg/m(2), respectively; P = .24), age (37.8 +/- 15.4 vs 50.3 +/- 17.7 months; P = .14), and sex. PWS and control groups also had equivalent fasting levels of total ghrelin (787 +/- 242 vs 716 +/- 135 pg/mL, respectively; P = .24), bioactive ghrelin (102 +/- 35 vs 91 +/- 23 pg/mL; P = .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls (r = -0.760, P = .029) but not PWS (r = 0.015, P = .97).Children5 years of age with PWS, who had not yet developed hyperphagia or excessive obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of older, hyperphagic people with PWS. It is possible that ghrelin levels increase suddenly before hyperphagia develops.

Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this study we examined the regulation of plasma ghrelin by fasting in genetically obese animals considering its molecular forms. Plasma levels of active form of ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice compared with those in their control mice. Zucker fatty (fa/fa) rats also showed lower plasma ghrelin levels by fasting than the control rats. Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats. Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats. The effect of the severity of obesity on secretory regulation of ghrelin was also studied. Older fatty rats showed low plasma ghrelin levels even after 48-h fasting. These data suggest that the short-term secretory regulation of total ghrelin and the active form of ghrelin is delayed in obese animals and that blood glucose levels may be involved in the delayed regulation.

OBJECTIVES Ghrelin and obestatin are 2 gastric hormones with opposite effects on food intake and body weight. We investigated plasma ghrelin and obestatin in children with failure to thrive (FTT) and obesity as compared with age-matched controls. METHODS A total of 63 children were included in the study: 13 with FTT, 17 with obesity, and 33 age-matched controls. Children fasted for at least 8 hours before specimen collection. Both hormones were measured using commercially available enzyme immunoassay kits. RESULTS Ghrelin and obestatin levels in children with FTT were not significantly different from that of the age-matched controls (P >0.05). In children with obesity, the total ghrelin levels were significantly lower (P = 0.0003) and the obestatin levels significantly higher (P = 0.029) compared with those in controls. In the control group, the fasting ghrelin level was significantly higher in the younger ( 3 years; P = 0.0004). Obestatin levels correlated positively with weight-for-age percentiles in the obese group (P = 0.011) and negatively in the control group >3 years (P = 0.019). CONCLUSIONS Compared with the levels in age-matched controls, fasting ghrelin and obestatin levels did not differ significantly in children with FTT. In the children with obesity, the decreased ghrelin and increased obestatin levels suggest a possible adaptive process to positive energy balance. Ghrelin had pronounced age-related changes, and obestatin was associated with the weight status. This may suggest that these 2 hormones use different mechanisms to regulate energy balance and weight.

BackgroundGhrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of AG and DAG.ObjectivesTo evaluate key pharmacokinetic parameters of AG, DAG, and total ghrelin in healthy men and women.MethodsIn study 1, AG (1, 3, and 5 μg/kg per h) was infused over 65 min in 12 healthy (8 F/4 M) subjects in randomized order. In study 2, AG (1 μg/kg per h), DAG (4 μg/kg per h), or both were infused over 210 min in ten healthy individuals (5 F/5 M). Plasma AG and DAG were measured using specific two-site ELISAs (study 1 and 2), and total ghrelin with a commercial RIA (study 1). Pharmacokinetic parameters were estimated by non-compartmental analysis.ResultsAfter the 1, 3, and 5 μg/kg per h doses of AG, there was a dose-dependent increase in the maximum concentration (Cmax) and area under the curve (AUC(0–last)) of AG and total ghrelin. Among the different AG doses, there was no difference in the elimination half-life, systemic clearance (CL), and volume of distribution. DAG had decreased CL relative to AG. The plasma DAG:AG ratio was ∼2:1 during steady-state infusion of AG. Infusion of AG caused an increase in DAG, but DAG administration did not change plasma AG. Ghrelin administration did not affect plasma acylase activity.ConclusionsThe pharmacokinetics of AG and total ghrelin appears to be linear and proportional in the dose range tested. AG and DAG have very distinct metabolic fates in the circulation. There is deacylation of AG in the plasma but no evidence of acylation.

The objective of this study was to evaluate and compare different sample treatments and storage conditions in order to determine optimal conditions for total and acylated canine ghrelin measurement using ELISA assays. Under the conditions assessed in this study, total ghrelin concentration was stable when stored at room temperature or under cooled conditions (4°C) for approximately six hours regardless of the type of anticoagulant used. When samples were stored at under −20°C, three freeze/thaw cycles during storage did not alter total ghrelin concentration if serum or plasma treated with EDTA or with EDTA-aprotinin is used. When samples were stored at under −80°C, no significant differences were observed after three freeze/thaw cycles in total ghrelin concentrations in serum or plasma treated with EDTA, EDTA-aprotinin or heparin. While acylated ghrelin showed to be very instable, its analysis should be performed within an hour of sample collection or stored at −80°C preferably in serum in order to acquire accurate data. Addition of HCl did not improve total or acylated ghrelin stability. Furthermore, acidification of plasma samples decreased the stability of total ghrelin and impeded determination of acylated ghrelin with the ELISA used in this study.