Ghrelin Concentrations Research Articles

Total sleep deprivation decreases saliva ghrelin levels in adolescents.

Ghrelin, a regulator of food intake and energy expenditure, has been shown to be associated with insufficient sleep. The goal of the present study was to investigate the effect of a single night of total sleep deprivation on fasting saliva ghrelin and on nocturnal variation of saliva ghrelin concentration. A further aim of the study was to investigate the influence of body mass index on changes in saliva ghrelin levels. Altogether 35 adolescents (18 boys; age: 13.8 ± 1.14 years) were studied on two subsequent days (sleep and total sleep deprivation). Saliva samples were collected during the two experimental nights at 21:00 hours, 01:00 hours and 06:00 hours. Total-ghrelin concentration showed a continuous increase from the evening until 06:00 hours. This increase was blunted significantly (p=0.003) by total sleep deprivation. Total-ghrelin level was significantly lower (p=0.02) during total sleep deprivation at 06:00 hours (median 403.6pg ml-1 ; 95% confidence interval: 343.1-468.9pg ml-1 ) as compared with values during the sleep condition (median 471.2pg ml-1 ; 95% confidence interval: 205.4-1578.7pg ml-1 ). Acyl-ghrelin levels did not present any change at the three time points, and were not affected by total sleep deprivation. Stratifying the study population according to body mass index (normal weight and overweight/obese groups), the blunting effect of total sleep deprivation was more pronounced in the obese/overweight group (sleep: median 428.2pg ml-1 ; 95% confidence interval: 331.3-606.9pg ml-1 versus total sleep deprivation: median 333.1pg ml-1 ; 95% confidence interval: 261.5-412.9pg ml-1 ; p=0.0479). Saliva total-ghrelin concentrations gradually increased during the night, and total sleep deprivation significantly blunted this increase. This blunting effect was mainly observed in subjects with overweight/obesity. The physiological and clinical implications of the present observation are to be clarified by further studies.

Effects of Helicobacter pylori Infection on Ghrelin and Insulin-like Growth Factor 1 Secretion in Children with Idiopathic Short Stature.

Background: A diagnosis of "idiopathic short stature" (ISS) in a child means that the cause of the disease has not been established, although there are certainly some unknown factors that contributed to its occurrence. Ghrelin and leptin are important in controlling food intake; ghrelin is also a growth hormone (GH) stimulator. Both enterohormones are produced in the stomach and their secretion may be affected by a Helicobacter pylori (H. pylori) infection. Methods: Our study included a group of 61 children (53 prepubertal and 8 peripubertal) with ISS, without any gastrointestinal tract symptoms but in whom the histopathological evaluation of stomach tissue was made during gastroscopy to diagnose H. pylori infection. In each child, fasting ghrelin, leptin and IGF-1 concentrations, and GH levels in two stimulation tests were assessed. Results: H. pylori infection was confirmed in 24.6% of the children. Ghrelin and IGF-1 concentrations were significantly lower in H. pylori-positive than H. pylori-negative children (this was more noticeable in prepubertal subgroups), however there was not a discrepancy in regards to GH concentrations in stimulation tests, leptin levels or the nutritional state between groups. Conclusions: Short children, infected by H. pylori seem to have lower ghrelin and IGF-1 concentrations than children without infection, this may be the reason for a worse growth rate in this subgroup.

Pharmacokinetics and Endocrine Effects of an Oral Dose of D-Pinitol in Human Fasting Healthy Volunteers.

The present study characterizes the oral pharmacokinetics of D-Pinitol, a natural insulin mimetic inositol, in human healthy volunteers (14 males and 11 females). D-Pinitol absorption was studied in (a) subjects receiving a single oral dose of 15 mg/kg (n = 10), or (b) 5 mg/kg pure D-Pinitol (n = 6), and (c) subjects receiving D-Pinitol as part of carbohydrate-containing carob pods-derived syrup with a 3.2% D-Pinitol (Dose of 1600 mg/subject, n = 9). The volunteers received a randomly assigned single dose of either D-Pinitol or carob pod-derived syrup. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180, 240, 360 and 1440 min after intake. Plasma concentration of D-Pinitol was measured and pharmacokinetic parameters obtained. The data indicate that when given alone, the oral absorption of D-Pinitol is dose-dependent and of extended duration, with a Tmax reached after almost 4 h, and a half-life greater than 5 h. When the source of D-Pinitol was a carob pods-derived syrup, Cmax was reduced to 40% of the expected based on the data of D-Pinitol alone, suggesting a reduced absorption probably because of competition with monosaccharide transport. In this group, Tmax was reached before that of D-Pinitol alone, but the estimated half-life remained the same. In the D-Pinitol groups, plasma concentrations of glucose, insulin, glucagon, ghrelin, free fatty acids, and pituitary hormones were additionally measured. A dose of 15 mg/kg of D-Pinitol did not affect glucose levels in healthy volunteers, but reduced insulin and increased glucagon and ghrelin concentrations. D-Pinitol did not increase other hormones known to enhance plasma glucose, such as cortisol or GH, which were surprisingly reduced after the ingestion of this inositol. Other pituitary hormones (gonadotropins, prolactin, and thyroid-stimulating hormone) were not affected after D-Pinitol ingestion. In a conclusion, D-Pinitol is absorbed through the oral route, having an extended half-life and displaying the pharmacological profile of an endocrine pancreas protector, a pharmacological activity of potential interest for the treatment or prevention of insulin resistance-associated conditions.

The Effects of 5-Hydroxytryptamine and Interaction With Kisspeptin in Controlling Ghrelin and Adiponectin Secretion

Introduction: 5-Hydroxytryptamine (5HT) and kisspeptin are satiety factors, and ghrelin and adiponectin are orexigenic peptides. In this study, the mediating role of 5HT in the effects of GPR54 receptor blocking on ghrelin and adiponectin secretion was investigated. Methods: Male Wistar rats weighing 220-250 g received saline, kisspeptin 10 (1 or 3 nmol), 5HT (2, 5 or 10 µg), kisspeptin plus 5HT, or peptide 234 (P234) plus 5HT via the third cerebral ventricle. Serum ghrelin and adiponectin concentrations were determined using the enzyme-linked immunosorbent assay method. Results: Kisspeptin or 5HT treatment significantly reduced serum concentrations of ghrelin and adiponectin in comparison with saline. The injection of 2 nmol of P234 + 5HT significantly reduced serum ghrelin concentration compared to the 5HT alone, kisspeptin alone, and kisspeptin + 5HT groups. Injections of either 1 or 2 nmol of P234 along with 5HT significantly declined the mean serum adiponectin level compared to rats received the kisspeptin plus 5HT. Conclusion: Kisspeptin/GPR54 signaling pathway may be a putative target in serotonergic neurons to control ghrelin and adiponectin secretion.

Relationship between psychological stress and ghrelin concentrations in pregnant women with overweight or obesity

Exposure to, perception of, and response to stress have all been shown to influence appetite and dietary behaviors in non-pregnancy human and animal studies, mediated in part by the appetite stimulating hormone ghrelin. Yet, the impact of prenatal stress on biological pathways associated with appetite in the context of pregnancy is not well understood. The objective of this study was to assess the relationship between these layered dimensions of stress with fasting and postprandial plasma ghrelin concentrations among Hispanic pregnant women with overweight or obesity, a population known to experience heightened levels of stress. Thirty-three non-diabetic Hispanic women with pre-pregnancy body mass index of 25.0–34.9 kg/m2 participated in a crossover study at 28–32 weeks’ gestation. At each visit, participants provided fasting blood and saliva samples, consumed a standardized mixed-meal, and completed a 15-minute task: friendly conversation (control) or the Trier Social Stress Test (experimental stress exposure). Six timed blood and saliva samples were collected up to 2 h from baseline and assayed for ghrelin and cortisol, respectively, and area-under-the-curve (AUC) values were computed. Day-to-day stress levels were assessed by the Perceived Stress Scale. Physiological and psychological stress reactivity was determined by cortisol AUC and change in self-reported affect state, respectively, during the experimental stress visit. Maternal perceived stress was positively associated with ghrelin concentrations in the fasted (β = 0.06, p = 0.02) and postprandial state (β = 0.05, p = 0.02). Mean ghrelin AUC was not significantly different following acute stress versus control. Measures of acute stress reactivity were not associated with ghrelin AUC. Contrary to our hypothesis, among Hispanic pregnant women with overweight and obesity, exposure to an acute stress induction task did not alter postprandial ghrelin concentrations, and changes in individual psychological and physiological stress reactivity did not associate with postprandial ghrelin. However, our findings suggest that maternal report of general perceived stress over the last month is associated with higher fasting and postprandial ghrelin concentrations. Differences in the effects of short-term stress exposure versus day-to-day perception of stress on appetite and food intake in pregnancy deserves further investigation.

PSVI-12 Ghrelin Plasm Concentrations are Greater in High- vs low-RFI Hampshire Male Lambs within a Transient Surge of Secretion Just Before a Scheduled Meal Feeding

Abstract The aim was to explore potential differences on ghrelin plasm concentrations between efficient and inefficient lambs within a transient surge of ghrelin secretion just before a scheduled meal feeding. Six high- (256±19 g) and six low-RFI (-242±19 g) Hampshire entire male lambs (Age=168±2 d and BW=63±5 kg) were taken out of 25 individuals in a 56-d GrowSafe SystemsÒ feeding trial. After a 10-d adaptation to a once-daily ad-libitum feed offering (0900 h), at d11 three lambs from each RFI group continued the once-daily feeding schedule (FED), whereas feed was withheld from the other three lambs (FAST) from each RFI group for 24-h (d11 to d12). Blood samples were collected via indwelling jugular catheter. In d11, ghrelin plasm concentrations were determined by ELISA in all animals at 0800, 0840, 0900, 1000 and 1100, and d12 at 0900, 1000 and 1100 in the FAST group. A linear model for repeated measures was adjusted with PROC MIXED of SAS. Plasm ghrelin levels began to increase at 0800, and RFI groups reached significant difference (P < 0.05) within both FED and FAST groups at 0840, with the greatest difference at peak concentrations at 0900 h (3.9±0.2 vs 2.4±0.2 and 3.9±0.2 vs 3.0±0.2 ng/ml for high vs low RFI, respectively). In the descendent phase of the curve for the FED group, one hour after feeding, ghrelin plasm concentration levels continued to be greater (P < 0.05) for high RFI vs low RFI animals and reached basal levels by 1100 h. For the FAST group, ghrelin concentrations continued to increase averaging maximum concentrations at the end of feed restriction, 0900 h of d12, being 4.9±0.2 ng/mL for the high RFI animals and 3.5±0.2 ng/mL for the low RFI ones. In conclusion, high RFI lambs show more pronounced transient surge of ghrelin secretion just before a scheduled meal feeding than low RFI lambs.

PSXV-1 Genetic Variants of the Ghrelin, Ghsr1a, Mboat4 and NPY Genes Related to Feed Efficiency Traits and Ghrelin Plasma Concentration in Hampshire Lambs

Abstract Reports in the literature suggest that a transient surge of ghrelin secretion (TSGS) just before a scheduled meal may be triggered by an appetite mechanism. Also, it is known that circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior. The aim of the present study was to search for genetic variants in five selected genes (GHRL, GHSR1a, MBOAT4, NPY and AgRP) within the ghrelin gene (GHRL) interaction network. gDNA was extracted from the six highest- and six lowest-RFI Hampshire non-castrated male lambs, out of a total of 25 lambs in a 56-d GrowSafe SystemsÒ feeding trial and the complete genes were amplified by PCR. Libraries were prepared and sequenced in the ILLUMINA platform MiniSeq Sequencing System. Variations were identified using the genomic variant call format (GVCF) workflow with HaplotypeCaller using the reference genome oviAri 4 - Oar_v4 (GCA_000298732.2). One hundred and ninety-two SNPs were found in the five analyzed genes. Most of them had been reported in the SNPs data base. Linear models including each SNP genotype at a time as fixed effects, in addition to ADG and mid test metabolic body weight as covariates for some variables, were adjusted. Forty-three of these SNPs had different genotype frequencies in the two RFI groups, and appear to be associated (p < 0.05) with traits such as RFI, feed intake (FI), feed conversion (FC) and ghrelin hormone concentration in plasma (GHRL) at the TSGS; especially SNPs rs399405301, rs421869734, rs604106535, rs417836509, rs600356564, rs590893697 at the MBOAT4 gene which resulted highly significant (p < 0.01) for RFI and GHRL. The SNP rs423156356 at the GHSR1a gene was highly significant (p < 0.01) for FI and FC. These SNPs (Table 1) have the potential to be used as genetic markers for improvement of feed efficiency in Hampshire sheep, but validation on a larger sample deserves further research efforts.

284 Gut and Skeletal Muscle Control the Effect of low Protein Diets on Feed Intake and Thermal Radiation of Broilers During Experimentally Induced Heat Stress

Abstract The objective of this study was to assess the effects of low protein diets on feed intake (FI), heat production and markers of FI and thermogenesis regulation in broilers under experimentally induced heat stress. Two-hundred-day-old broiler chicks were weight-matched and assigned into 36 pens (5-6 chicks/pen) followed by assigning them into two treatments (18 pens/treatment): 1) thermoneutral (TN), 2) heat stress (HS). Within each treatment, the pens were randomized to receive two diets (9 pens/diet): 1) normal protein (NP), 2) low protein (LP). The study lasted 6 weeks with 2 weeks of acclimation and 4 weeks of data collection. On week 6, birds were euthanized, and blood and tissue samples collected. All data were analyzed with either GLM or mixed procedure (SPSS). The student’s t-test was used to separate means between NP and LP diets within each treatment. There was no difference in average daily gain between NP and LP diets in the TN group, but LP decreased that during HS (P< 0.05). In TN condition, LP tended to increase the average daily feed intake (ADFI) compared to NP (P< 0.1), while during HS, LP was not different from NP in terms of ADFI (P>0.05). In TN condition, LP had a higher thermal radiation than NP, but LP had less thermal radiation than NP during HS (P< 0.05). In support of ADFI data, LP had a greater ghrelin transcript in the duodenum than NP in TN condition (P< 0.05). However, during HS, LP tended to decrease the plasma ghrelin concentration compared with NP (P< 0.1). Unlike TN condition, LP had a decreased muscle sirtuin and cytochrome c oxidase transcript than NP during HS (P< 0.05). Our data provide evidence that low protein diets mitigate the negative outcome of heat stress by reducing feed intake and heat production, which are regulated through genes expressed in the gut and skeletal muscle.

PSIX-9 The Effect of Endophyte-Infected Tall Fescue Seed Consumption on gut and Satiety Hormones Related to Intake in Holstein Steers

Abstract The objective of this study was to evaluate the impact of endophyte-infected tall fescue (E+) seed, and ergovaline (ERV), on gut and satiety hormones and investigate changes in post-absorptive metabolism. Holstein steers (n=12; 260 ± 16 kg) were assigned to one of three treatments (ERV concentration in diet dry matter): 0, 1.8, and 2.7 ppm with animals being adapted to an indoor environment for 4 days followed by a 7-day diet adaptation and a 10-day treatment period. On days 16 and 17, blood was collected via jugular catheters at 20-min intervals for 8 hours beginning 1 hour pre-feeding. Plasma was extracted and analyzed for insulin, leptin, and active ghrelin. Non-esterified fatty acids (NEFA), b-hydroxybutyrate (BHB), and glucose were analyzed to evaluate changes in postabsorptive metabolism using plasma from each 60-min interval. DMI decreased linearly with increased ERV concentration (P< 0.0001). A quadratic increase was observed for insulin with the 2.7 ppm ERV treatment having the greatest concentrations (P< 0.0001). A quadratic response was observed for leptin where the 1.8 ppm ERV treatment had the greatest concentrations (P< 0.0001). Active ghrelin concentrations decreased linearly with increasing ERV concentrations (P=0.047). A treatment-by-time interaction was observed for NEFA (P< 0.0001) where the 1.8 ppm ERV decreased from pre-feeding to 1-hour post-feeding and did not differ from control thereafter whereas, the 2.7 ppm ERV treatment increased above the 0 ppm ERV treatment beginning 5 hours post-feeding and was greatest among all treatments at 6 hours post-feeding. The 2.7 ppm ERV treatment exhibited the least BHB concentrations (P=0.029). Glucose concentrations increased linearly with increasing ERV concentrations (P=0.046). These results indicate that consumption of E+ seed decreases intake which may be possible through alteration of hormones and may also alter post-absorptive metabolism.

Does the timing of pasture allocation affect rumen and plasma metabolites and ghrelin, insulin and cortisol profile in dairy ewes?

A study was undertaken to assess the impact of the timing of grazing on rumen and plasma metabolites and some metabolic hormones in lactating dairy sheep allocated to an Italian ryegrass (Lolium multiflorum Lam) pasture in spring for 4 h/d. Twenty-four mid lactation Sarda ewes stratified for milk yield, body weight, and body condition score, were divided into four homogeneous groups randomly allocated to the treatments (2 replicate groups per treatment). Treatments were morning (AM, from 08:00 to 12:00) and afternoon pasture allocation (PM, from 15:30 to 19:30). Samples of rumen liquor (day 39) and blood plasma (days 17 and 34 of the experimental period) were collected before and after the grazing sessions. Moreover, on days 11 and 35, grazing time was assessed by direct observation and herbage intake measured by the double weighing procedure. Grazing time was longer in PM than AM ewes (P < 0.001) but herbage intake was undifferentiated between groups. The intake of water-soluble carbohydrates at pasture was higher in PM than AM ewes (P < 0.05). The post-grazing propionic and butyric acid concentration, as measured on day 39, were higher in PM than AM ewes (P < 0.05). The basal level of glucose on day 34 and insulin (on both sampling days) were higher in PM than AM (P < 0.05). The opposite trend was detected for non-esterified fatty acids (P < 0.05, day 34) and urea (both days). Pasture allocation in the afternoon rather than in the morning decreased plasma concentration of ghrelin (P < 0.001) and cortisol (P < 0.001), with a smoothed trend on day 34 in the latter variable. To conclude, postponing the pasture allocation to afternoon increased the intake of WSC, favoring a glucogenic pattern of rumen fermentation and a rise of glucose and insulin levels in blood, although these effects were not consistent across the whole experimental period. Moreover, the afternoon grazing decreased the level of cortisol and ghrelin, suggesting a higher satiation-relaxing effect.

Ghrelin and Obestatin in Adolescent Patients with Anorexia Nervosa: Is There an Association with Disordered Eating, Depression, and Obsessive-Compulsive Symptoms?

Anorexia nervosa (AN) is an eating disorder characterized by restrictive eating and significant weight loss. In the course of AN, changes are observed in appetite regulation, including orexigenic ghrelin and potentially anorexigenic obestatin. The study aimed to determine if any changes in serum ghrelin and obestatin levels during treatment of AN are observed, while investigating the correlations between these peptides and the severity of disturbed eating attitudes, depression, and anxiety. Thirty adolescent inpatients with AN (examined twice: before hospitalization treatment AN-BT and after treatment AN-AT) and thirty healthy age- and height-matched girls (CG) participated in the study. Anthropometric, serum ghrelin and obestatin concentrations and psychometric evaluations (Eating Attitudes Test 26 Item-EAT-26, Beck Depression Inventory-BDI, Hamilton Depression Rating Scale-HDRS, and Yale Brown Obsessive-Compulsive Scale-Y-BOCS) were performed. The study revealed significantly higher ghrelin and obestatin levels in AN-BT than in AN-AT. A trend toward lower levels during treatment provided partial normalizations. Analyzing correlations in the AN-BT vs. CG group, correlations of peptides with EAT-26, BDI, and HDRS scores were detected. These results suggest a potential role for ghrelin and obestatin in the context of defense mechanisms regulating appetite and body weight in the course of AN and in terms of psychopathological changes co-occurring with this eating disorder.

The Levels of Ghrelin, Glucagon, Visfatin and Glp-1 Are Decreased in the Peritoneal Fluid of Women with Endometriosis along with the Increased Expression of the CD10 Protease by the Macrophages.

The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages.

GHRELIN LEVEL CHANGES IN HUMANS WITH TYPE 2 DIABETES MELLITUS AND OBESITY

Purpose: The aim of the research was to identify the plasma ghrelin concentration in humans with Type 2 Diabetes mellitus and obesity and to investigate a statistically significant relation between plasma ghrelin levels and other important metabolic factors in Type 2 Diabetes mellitus and obesity pathogenesis.

The Impact of Gestational Diabetes Mellitus on Human Milk Metabolic Hormones: A Systematic Review.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with short- and long-term health consequences for the infant and mother. Breastfeeding is the recommended mode of feeding as it offers an opportunity to reduce the risk of GDM consequences, likely partially mediated through changes in human milk (HM) composition. This review systematically reviewed 12 identified studies that investigated the impact of GDM on concentrations of HM metabolic hormones. Meta-analysis was not possible due to significant heterogeneity in study designs and hormone measurement techniques. The risk of bias was assessed using the National Institute for Clinical Excellence (NICE) tool. The methodological qualities were medium in half of the studies, while 25% (3/12) of studies carried a high risk of bias. Significant relationships were reported between GDM and concentrations of HM ghrelin (3/3 studies), insulin (2/4), and adiponectin (2/6), which may play an integral role in infant growth and development. In conclusion, preliminary evidence suggests that GDM may alter HM metabolic hormone concentrations; however, these relationships may be limited to the early lactation stage.

Objective and Subjective Appetite Assessment in Patients with Gynecological Cancer: A Pre- and Post-Operative Pilot Study.

Although appetite and its disorders have been implicated in disease progression and outcomes, ghrelin concentrations, an objective appetite measure, are rarely assessed in patients with gynecological malignancies. The present study aimed to assess changes in post-operative versus pre-operative appetite levels in patients with gynecological cancers scheduled for tumor removal surgery (N = 53). Acylated ghrelin concentrations were assessed as an objective appetite proxy, whereas the Council of Nutrition appetite questionnaire (CNAQ) was employed as a subjective appetite measure. Ghrelin concentrations were increased post-operatively (median: 12.1 pg/mL, IQR: 0.67 to 23.5, p-value = 0.001) but the perceived appetite of patients (CNAQ) remained unchanged (median: −1, IQR: −3 to 1). Tumor removal surgery decreased all anthropometric indices (body weight, body mass index, waist and hips circumferences, triceps skinfolds, body fat, fat mass and fat mass index, p-value ≤ 0.001 for all) and doubled the risk of malnutrition among patients. No difference was recorded in the change in participants’ objective and subjective appetite when they were classified according to the tumor type. No correlation was observed between ghrelin concentrations and CNAQ score pre-operatively (Spearman’s rho correlation coefficient = −0.181, p-value = 0.298) or post-operatively (Spearman’s rho correlation coefficient = 0.071, p-value = 0.684). The observed post-operative rise in ghrelin concentrations is associated with body weight loss and consists of a possible defense mechanism of the human body, aiming to prolong survival.

A Randomized Trial of the Effect of a GnRH Analogue Injection on Ghrelin Levels in Girls

Introduction: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels. Methods: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH^® (100 μg/m²) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels. Results: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 ± 257.1 vs. 247.6 ± 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5–115.7] vs. 143.5 [71.4–285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = −0.73, p = 0.005, and r = −0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = −0.57, p = 0.041). Conclusion: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels.

Dietary acid load modifies the effects of ApoA2–265 T > C polymorphism on lipid profile and serum leptin and ghrelin levels among type 2 diabetic patients

This investigation with aimed the effect of APOA2–265 T > C polymorphism and dietary acid load (DAL) as either potential renal acid load (PRAL) and net endogenous acid production (NEAP) intake interaction on metabolic markers in type 2 diabetes mellitus (T2DM). In present cross-sectional study, 737 patients with T2DM (290 men and 447 women) were enlisted from diabetes centers in Tehran. The dietary intakes of all participants during the last year was acquired by a validated semi-quantitative food frequency (FFQ) questionnaire. Polymerase chain reaction (PCR) was used for genotyping the APOA2–265 T > C. Biochemical indises containing leptin, ghrelin, total cholesterol (Bailey et al., J Clin Invest 97:1147–1453, 1996), low-density lipoprotein cholestrol (LDL-C), high-density lipoprotein cholestrol (HDL-C), triglyceride (TG), superoxide dismutase (SOD), high sensitivy C-reactive protein (hs-CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), prostaglandin F2α (PGF2α) and interleukin 18 (IL18) were measured by standard method. Atherogenic indices (AIP, AC, CR-I, CR-II) were calculated. The gene-diet interactions were evaluated using an GLM. The frequency overall prevalence of rs5082 genotypes was 63.82 and 36.17% for T-allele and C-allele respectively. TG, Ghrelin, and hs-CRP concentrations were significantly higher among carriers with C allele than TT homozygotes. However, TC/CC genotypes have lower PTX3 than TT homozygotes (P < 0.05). C-allele carriers had highest mean of BMI (PNEAP=0.04, PPRAL = 0.006), WC (PNEAP=0.04, PPRAL = 0.04), TC (PNEAP=0.03, PPRAL = 0.01), ghrelin (PNEAP=0.01, PPRAL = 0.04), and leptin (PNEAP=0.04, PPRAL = 0.03) when placed in top tertiles of NEAP and PRAL.BMI, WC, TC, ghrelin, and leptin levels may be modified in C carriers by decreasing DAL, though, further investigations are required to confirm these findings.

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

ObjectiveTo 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). MethodsEight 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. ResultsEA 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. ConclusionEA 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.

Body Temperature Patterns and Energy Balance Hormones in Free-Living Thirteen-Lined Ground Squirrels (Ictidomys tridecemlineatus) from Different Latitudes.

AbstractThis article examines hormone concentrations and body temperature (Tb) patterns of free-living thirteen-lined ground squirrels (TLGSs) across the majority of their latitudinal range in the United States (from Texas to Minnesota). Free-living TLGSs () were implanted with Tbdata loggers in 2019 before they entered hibernation. Three adult female TLGSs, one each from Oklahoma (low latitude), Iowa (middle latitude), and Minnesota (high latitude), were recaptured in 2020 after the hibernation season. Although this provides an n of 1 for each location and therefore no statistically supported conclusions can be drawn, the hibernation season was longest in the animal from the highest latitude with coldest winter soil temperatures (Minnesota) and shortest in the animal retrapped at the lowest latitude (Oklahoma). Torpor bouts were generally longer when soil temperatures were lower. The Iowa and Minnesota squirrels had a prolonged period of short torpor bouts with Tb near 20°C at the beginning of the hibernation season. Concentrations of the orexigenic hormone ghrelin and the sex hormones estradiol and testosterone were also compared in populations from different latitudes. In general, Minnesota males had higher testosterone than males from other populations, possibly due to a later breeding season relative to other squirrel populations. Animals trapped in early summer had significantly lower concentrations of ghrelin than those captured in midsummer, potentially driving the fat-storing period before the hibernation season. Together, these results suggest latitudinal variation in physiological regulation of circannual rhythms.

Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUNDBiliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development.AIMTo determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODSThis was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov–Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used.RESULTSPatients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage.CONCLUSIONPossible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.