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

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

Associations of Stress and Appetite Hormones with Binge Eating in Females with Anorexia Nervosa after Weight Restoration: A Longitudinal Study

Binge eating is a transdiagnostic eating disorder symptom that can occur in patients with anorexia nervosa (AN), persisting after weight restoration, and impeding their recovery. However, little is known about the biological predictors of binge eating after AN weight restoration. The goals of this exploratory study of 73 females with AN were: (1) to examine changes in cortisol, the adrenocorticotropic hormone, norepinephrine, ghrelin (total and active), and leptin levels across the admission, discharge, and 3 months post-discharge from the inpatient AN weight restoration; and (2) to determine whether the target hormones were associated with objective or subjective binge eating (OBE or SBE). The participants completed the self-reported Eating Disorder Examination Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory-II, and provided fasting whole blood samples for hormone assays. The results showed significant changes in body mass index (BMI), cortisol, total ghrelin, and leptin levels over the three time points. The cortisol levels at admission and discharge were significantly associated with the number of SBE episodes at 3 months post-discharge. Findings suggest the need to replicate and confirm the role of cortisol in predicting the emergence of SBE and uncover the mechanisms underlying SBE and cortisol to prevent SBE and its negative consequences.

Is ghrelin a biomarker of early-onset scoliosis in children with Prader–Willi syndrome?

Background Adolescents with idiopathic scoliosis display high ghrelin levels. As hyperghrelinemia is found in patients with PWS and early-onset scoliosis (EOS) is highly prevalent in these patients, our aims were to explore (1) whether ghrelin levels differ between those with and without EOS and correlate with scoliosis severity, and (2) whether ghrelin levels in the first year of life are associated with the later development of EOS. Methods We used a case control study design for the first question and a longitudinal design for the second. Patients with PWS having plasma ghrelin measurements recorded between 2013 and 2018 in our database were selected and 30 children < 10 years old with EOS and 30 age- and BMI-matched controls without EOS were included. The Cobb angle at diagnosis was recorded. In addition, 37 infants with a ghrelin measurement in the first year of life were followed until 4 years of age and assessed for EOS. Total ghrelin (TG), acylated (AG) and unacylated ghrelin (UAG), and the AG/UAG ratio were analyzed. Results EOS children had an AG/UAG ratio statistically significantly lower than controls. The Cobb angle was positively correlated with TG and UAG. TG and AG in the first year of life were higher in infants who later develop EOS without reaching a statistically significant difference. Conclusions Our results suggest that ghrelin may play a role in the pathophysiology of EOS in PWS. Higher ghrelinemia in the first year of life required careful follow-up for EOS.

Free triiodothyronine (T3) is negatively associated with fasting ghrelin serum levels in a population sample of euthyroid subjects

Purpose Ghrelin is an orexigenic peptide hormone secreted in times of stress and hunger. It is deeply involved in the regulation of metabolism and energy homeostasis, promoting energy intake and inhibiting energy expenditure on a metabolic level. In this regard, it has in many ways antagonistic effect on the thyroid hormones, which increase metabolism and thus energy expenditure. While there is reasonable evidence of a negative association between ghrelin and hormones of the hypothalamic-pituitary-thyroid (HPT-) axis from studies in patients with thyroid dysfunction and small intervention studies, large-scale studies in healthy subjects are lacking. Therefore, we studied the relationship between total ghrelin serum levels and serum levels of the thyroid hormones in a large sample of euthyroid subjects. Methods Total ghrelin, thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined after an overnight fast in 1666 subjects participating in a population-based cross-sectional study (‘LIFE’) including 10,000 adults. 1012 subjects were included in this analysis. Multiple linear regression analyses were performed. Results FT3 was negatively associated with serum ghrelin; total sample: β = − 0.0001, p < 0.001; men: β = − 0.0002, p = 0.013; women: β = − 0.0001, p = 0.010, adjusted for age, BMI, alcohol consumption, serum levels of TSH and fT4 and smoking status. No associations were found between ghrelin serum levels and serum levels of fT4 or TSH. Conclusion This is to date the largest study investigating the relationship between total serum ghrelin and thyroid hormones. The results point to a complex interaction and should initiate further research.

Beneficial Potential of Banha-Sasim-Tang for Stress-Sensitive Functional Dyspepsia via Modulation of Ghrelin: A Randomized Controlled Trial

Background: Functional dyspepsia (FD) is a highly complex pathophysiologic disease, which shows low recovery and high relapse rates. Therefore, a growing number of clinicians and patients are looking for alternative herbal medicine. Banha-Sasim-Tang (BST) is an herbal prescription for treating a wide range of dyspepsia in traditional Korean medicine (TKM).Aim of the study: This study aimed to evaluate the efficacy of BST on FD in patients with psychological stress-related symptoms and to investigate the involvement of ghrelin. This study is registered at https://cris.nih.go.kr/with the identification number KCT 0002811.Materials and methods: A total of 31 participants with FD who met the Rome IV criteria and the psychological stress-related pattern were enrolled in a double-blind, randomized, and controlled study. Participants were randomly assigned to the BST group (10 g twice daily for 4 weeks) or placebo group. The primary endpoint was a change in the Nepean Dyspepsia Index–Korean (NDI-K) score. The secondary endpoints were changes in the Visual Analog Scale (VAS) scores and plasma ghrelin level.Results: All participants completed the study (n = 15 for BST, n = 16 for placebo). BST decreased NDI-K scores compared with placebo, but the difference was not statistically significant (37.40 ± 27.40 vs 22.50 ± 23.85, p = 0.12). VAS scores and plasma total ghrelin levels were significantly improved in patients who were treated with BST (3.19 ± 1.60 vs 1.38 ± 2.85, p = 0.03 for VAS and 105.69 ± 287.89 vs -142.31 ± 314.32, p = 0.03 for total ghrelin). No BST-related adverse effects were observed during the trial.Conclusion: Our results indicate the clinical potential of BST for FD patients and are the first study to show the modulation of plasma ghrelin as one of its corresponding mechanisms.Clinical Trial Registration:https://cris.nih.go.kr/, identifier KCT 0002811.

Influence of Menstrual Cycle or Hormonal Contraceptive Phase on Energy Intake and Metabolic Hormones—A Pilot Study

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 < 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.

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY.Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes.Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months.Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain.Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet.Clinical Trial Registry:ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).

The Effect of COVID-19 Infection on Human Blood Ghrelin Hormone: A Pilot Study

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.

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.