The milk study protocol: A longitudinal, prospective cohort study of the relationship between human milk metabolic hormone concentration, maternal body composition, and early growth and satiety development in Samoan infants aged 1-4 months.

BACKGROUND: Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety. METHODS: We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim. DISCUSSION: This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity.

Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY). Changes were considered important if p < 0.100 and the effect size was ≥medium. There appeared to be a three-way (group x phase x time) interaction for acylated ghrelin where concentrations appeared to be greater in USERS versus NON-USERS during the OP 90-min post-prandial and during the LP fasted, and 90-min post-prandial. In USERS, ghrelin appeared to be greater 90-min post-prandial in the OP versus the FP with no other apparent differences between phases. There were no apparent differences between phases in NON-USERS. There appeared to be a three-way interaction for PYY where concentrations appeared to be greater in USERS during the FP 60-min post-prandial and during the OP 30-min post-prandial. In USERS PYY appeared to be greater 60-min post-prandial during the OP versus the LP with no other apparent differences. There were no apparent differences between phases in NON-USERS. There appeared to be no effect of group or phase on GLP-1, or appetite perceptions. These data demonstrate small effects of menstrual cycle phase and oral contraceptive use on the acylated ghrelin and total PYY response to a standardized meal, with no effects on active GLP-1 or perceived appetite, though more work with a large sample size is necessary.

Effects of Wheat Biscuits Enriched with Plant Proteins Incorporated into an Energy-Restricted Dietary Plan on Postprandial Metabolic Responses of Women with Overweight/Obesity.

This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake.

[Serum ghrelin changes after bariatric surgery]. / Kak izmenyaetsya uroven' grelina u patsientov, perenesshikh bariatricheskie vmeshatel'stva.

OBJECTIVE: To study the effect of bariatric surgery on serum ghrelin in patients with morbid obesity. MATERIAL AND METHODS: We experimentally analyzed serum ghrelin in 96 rats. Of these, 84 rats underwent sleeve gastrectomy, and 12 rats comprised the control group (no surgery). We measured body weight and serum ghrelin using ELISA method after 1, 3, 7, 14, 21 and 30 days after surgery. Serum ghrelin was studied before and after bariatric surgery in 23 patients with morbid obesity. RESULTS: Baseline serum ghrelin was lower in larger rats and obese patients compared to normal body weight. We found no decrease in serum ghrelin after resection of fundal ghrelin-releasing part of the stomach. CONCLUSION: Stomach volume changes after restrictive bariatric surgery (sleeve resection or gastroplication) are accompanied by mild increase in serum ghrelin. This increment is greater after more significant body weight loss after surgery. Similar researches will help to find new treatment strategies for pathological obesity.

Ghrelin proteolysis increases in plasma of men, but not women, with obesity.

AIMS: Since plasma ghrelin can undergo des-acylation and proteolysis, the aim of this study was to investigate the extent to which an enhancement of these reactions is associated to the decrease of ghrelin in plasma after food intake or in individuals with obesity. MAIN METHODS: we performed an intervention cross-sectional study, in which levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n = 21 males) with normal weight (NW, n = 20) or overweight/obesity (OW/OB, n = 20). KEY FINDINGS: Preprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was ∼4.6-fold higher in plasma of males with OW/OB. In males, ghrelin proteolysis positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with OW/OB, but preprandial ghrelin proteolysis was not different between females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially ∼2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes. SIGNIFICANCE: Current study shows that ghrelin proteolysis increases in males with obesity as well as after meal in lean individuals. Therefore, ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.

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

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

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

Lower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

Objective: Roux-en-Y gastric bypass is an effective intervention for metabolic disorder. We aim to elucidate whether ghrelin contributes to weight reduction, and glycemic and lipid control after Roux-en-Y gastric bypass (RYGB). Design: Four-week-old WT and Ghrl-TSC1-/- mice were fed high fat diet for 12 weeks before surgery, and continued to be on the same diet for 3 weeks after surgery. Body weight, food intake, glycemic and lipid metabolism were analyzed before and after surgery. Results: Gastric and circulating ghrelin was significantly increased in mice with RYGB surgery. Hypoghrelinemia elicited by deletion of TSC1 to activate mTOR signaling in gastric X/A like cells demonstrated no effect on weight reduction, glycemic and lipid control induced by Roux-en-Y gastric bypass surgery. Conclusion: Lower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

Impaired Brain Satiety Responses After Weight Loss in Children With Obesity.

CONTEXT: Obesity interventions often result in increased motivation to eat. OBJECTIVE: We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT). METHODS: Neuroimaging and hormone assessments were conducted before and after 24-week FBT intervention in children with obesity (OB, n = 28), or children of healthy weight without intervention (HW, n = 17), all 9- to 11-year-old boys and girls. We evaluated meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions and gut hormones. RESULTS: Among children with OB who underwent FBT, greater declines of BMI z-score were associated with lesser reductions after the FBT intervention in meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions (P < 0.05), and the slope of relationship was significantly different compared with children of HW. In children with OB, less reduction in brain responses to a meal from before to after FBT was associated with greater meal-induced reduction in ghrelin and increased meal-induced stimulation in peptide YY and glucagon-like peptide-1 (all P < 0.05). CONCLUSION: In response to FBT, adaptations of central satiety responses and peripheral satiety-regulating hormones were noted. After weight loss, changes of peripheral hormone secretion support weight loss, but there was a weaker central satiety response. The findings suggest that even when peripheral satiety responses by gut hormones are intact, the central regulation of satiety is disturbed in children with OB who significantly improve their weight status during FBT, which could favor future weight regain.

EFFECT OF 20-HOUR FASTING AND LOW FAT DIET ON GHRELIN HORMONE, GLUCOSE LEVEL AND LIVER FUNCTION IN ALBINO RATS MALE.

OBJECTIVE: The aim: It aims to study the effect of fasting and low fat diet on ghrelin hormone, glucose level, the liver enzymes AST and ALT. PATIENTS AND METHODS: Materials and methods: The experimental study was conducted using 24 healthy young male albino rat weighing 95±5 gram and age 2 month, one-way (ANOVA) were employed to determine a significance of differences. RESULTS: Results: A significant increase p≤0.05 in glucose level of non-fasting control group compere with non-fasting low fat diet group, significant increase p≤0.05 in glucose level of control group fasting for 20h compared with low fat diet fasting for 20h group, significant decrease p≤0.05 when compares non-fasting low fat diet compares to 20h fasting low fat diet and significant decrease p≤0.05 when compares non-fasting control compares to 20h fasting control, while the effect of fasting and low fat diet on ghrelin hormone. A significant decrease p≤0.05 in ghrelin hormone level of non-fasting control group compere with non-fasting low fat diet group, significant increase p≤0.05 in ghrelin hormone of control group fasting for 20h compared with low fat diet fasting for 20h group, non-fasting control compares to 20h fasting control show a significant (p≤0.05) increase, Fasting with low fat diet cause a significant decrease p≤0.05 in ALT level, also in AST level there was a significant decrease p≤0.05 after 20h fasting. CONCLUSION: Conclusions: The fasting and low fat diet have effected on ghrelin hormone, glucose level and fasting with low fat diet cause decrease in ALT level, also in AST level decrease after 20h fasting in male albino rats.

Basal blood concentrations of some orexigenic and anorexigenic hormones in obese and nonobese individuals according to blood groups.

OBJECTIVE: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups. PATIENTS AND METHODS: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants. RESULTS: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded. CONCLUSIONS: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.

Energetic demands of lactation produce an increase in the expression of growth hormone secretagogue receptor in the hypothalamus and ventral tegmental area of the rat despite a reduction in circulating ghrelin.

Lactating rats show changes in the secretion of hormones and brain signals that promote hyperphagia and facilitate the production of milk. Little is known, however, about the role of ghrelin in the mechanisms sustaining lactational hyperphagia. Here, we used Wistar female rats that underwent surgery to sever the galactophores to prevent milk delivery (GC rats) and decrease the energetic drain of milk delivery. We compared plasma acyl-ghrelin concentrations and growth hormone secretagogue receptor (GHSR) mRNA expression in different brain regions of GC rats with those of sham operated lactating and nonlactating rats. Additional lactating and nonlactating rats were implanted with cannulae aimed at the lateral ventricles and were used to compare feeding responses to central ghrelin or GHSR antagonist infusions to those of nonlactating rats receiving similar infusions on day 14-16 postpartum (pp). Results show lower plasma acyl-ghrelin concentrations on day 15 pp sham operated lactating rats compared to GC or nonlactating rats. These changes occur in association with increased GHSR mRNA expression in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA) of sham operated lactating rats. Despite lactational hyperphagia, infusions of ghrelin (0.25 or 1 µg) resulted in similar increases in food intake in lactating and nonlactating rats. In addition, infusions of the GHSR antagonist JMV3002 (4 µg in 1 µl of vehicle) produced greater suppression of food intake in lactating rats than in nonlactating rats. These data suggest that, despite lower plasma ghrelin, the energetic drain of lactation increases sensitivity to the orexigenic effects of ghrelin in brain regions important for food intake and energy balance, and these events are associated with lactational hyperphagia.

Effect of the liquid form of traditional Chinese medicine, Hozen-S, on gastric motility in dogs.

Juzen-taiho-to, a traditional Chinese herbal medicine, is used for patients with anorexia and fatigue in human medicine. In our previous study, granulated Juzen-taiho-to improved vincristine-induced gastrointestinal adverse effects through increasing gastric motility in dogs. As the effect of Hozen-S, the sweet liquid form of Juzen-taiho-to, on dog gastric motility has not been investigated, we examined the effect of administration of Hozen-S on gastric motility. Furthermore, we assessed dog plasma ghrelin level to further elucidate the mechanism of the effect of Hozen-S on gastric contraction. Finally, we assessed the palatability of Hozen-S compared to granulated Juzen-taiho-to and its effect on body weight in dogs. Administration of Hozen-S significantly increased gastric motility, plasma ghrelin concentration, and body weight. A palatability evaluation revealed that the dogs preferred Hozen-S to granulated Juzen-taiho-to. In conclusion, Hozen-S administration to dogs promoted gastric motility by raising plasma ghrelin levels. Considering these functional and palatability data, Hozen-S may replace granulated type Juzen-taiho-to and become a prominent traditional Chinese veterinary medicament.

Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis.

Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. This meta-analysis aimed to investigate the potential differences in plasma acyl ghrelin (AG) and des-acyl ghrelin (DAG) concentrations between normal weight and obese adults. Systematic literature searches of PubMed, Embase and Web of Science through October 2021 were conducted for articles reporting AG or DAG levels in obesity and normal weight, and 34 studies with 1863 participants who met the eligibility criteria were identified. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to evaluate group differences in circulating AG and DAG levels. Pooled effect size showed significantly lower levels of baseline AG (SMD: - 0.85; 95% CI: - 1.13 to - 0.57; PSMD < 0.001) and DAG (SMD: - 1.06; 95% CI: - 1.43 to - 0.69; PSMD < 0.001) in obese groups compared with healthy controls, and similar results were observed when subgroup analyses were stratified by the assay technique or storage procedure. Postprandial AG levels in obese subjects were significantly lower than those in controls when stratified by different time points (SMD 30 min: - 0.85, 95% CI: - 1.18 to - 0.53, PSMD < 0.001; SMD 60 min: - 1.00, 95% CI: - 1.37 to - 0.63, PSMD < 0.001; SMD 120 min: - 1.21, 95% CI: - 1.59 to - 0.83, PSMD < 0.001). In healthy subjects, a postprandial decline in AG was observed at 120 min (SMD: - 0.42; 95% CI: - 0.77 to - 0.06; PSMD = 0.021) but not in obese subjects (SMD: - 0.28; 95% CI: - 0.60 to 0.03; PSMD = 0.074). The mean change in AG concentration was similar in both the obese and lean health groups at each time point (ΔSMD30min: 0.31, 95% CI: - 0.35 to 0.97, PSMD = 0.359; ΔSMD60min: 0.17, 95% CI: - 0.12 to 0.46, PSMD = 0.246; ΔSMD120min: 0.21, 95% CI: - 0.13 to 0.54, PSMD = 0.224). This meta-analysis strengthens the clinical evidence supporting the following: lower baseline levels of circulating AG and DAG in obese individuals; declines in postprandial circulating AG levels, both for the healthy and obese individuals; a shorter duration of AG suppression in obese subjects after meal intake. These conclusions have significance for follow-up studies to elucidate the role of various ghrelin forms in energy homeostasis.

Are Peripheral Biomarkers Determinants of Eating Styles in Childhood and Adolescence Obesity? A Cross-Sectional Study.

Disturbances in eating behaviors have been widely related to obesity. However, little is known about the role of obesity-related biomarkers in shaping habitual patterns of eating behaviors (i.e., eating styles) in childhood. The objective of the present study was to explore the relationships between several biomarkers crucially involved in obesity (ghrelin, insulin resistance, and leptin/adiponectin ratio) and eating styles in children and adolescents with obesity. Seventy participants aged between 8 and 16 (56.2% men) fulfilled the Spanish version of the Dutch Eating Behavior Questionnaire for Children to measure external, emotional, and restrained eating styles. In addition, concentrations of ghrelin, leptin, adiponectin, insulin, and glucose were obtained through a blood test. Hierarchical multiple regression analyses controlling for age and sex were computed for each eating style. Results indicated that individuals with higher ghrelin concentration levels showed lower scores in restrained eating (ß = -0.61, p < 0.001). The total model explained 32% of the variance of the restrained pattern. No other relationships between obesity-related biomarkers and eating behaviors were found. This study highlights that one of the obesity-risk factors, namely lower plasma ghrelin levels, is substantially involved in a well-known maladaptive eating style, restraint eating, in childhood obesity.

Effect of nutrition status and inflammatory stimuli on ghrelin and peptide-YY levels among critically ill children: A prospective and observational study.

BACKGROUND: Ghrelin and peptide-YY (PYY) are two gut peptides with apparent opposing actions. In normal conditions, ghrelin and PYY work together in synergy to regulate energy homeostasis. During critical illness, series of metabolic, endocrine, and inflammatory changes take place in response to a severe insult. Emerging studies recorded alterations in gut hormone levels in critically ill adults. This study aims to assess the effect of inflammation, nutrition, and feeding status on ghrelin and PYY levels in critically ill children. METHODS: In this prospective study, we collected blood samples from critically ill children on days 2 or 3 of pediatric intensive care unit (PICU) admission for the analysis of serum ghrelin, PYY, and inflammatory markers. Data related to the intake anthropometry, as well as other clinical data, were collected from patients' records. Multiple linear regression analysis was used to identify factors affecting serum levels of these hormones. RESULTS: Forty-two children admitted to the PICU were included in this study. Ghrelin level was influenced by admission nutrition status of the children and age. PYY was influenced by macronutrient intake and age. Inflammatory markers also showed an association with the measured levels of these hormones, with C-reactive protein being positively associated with ghrelin levels and tumor necrosis factor alpha showing a positive association with PYY levels. CONCLUSION: Although ghrelin and PYY have been linked to feeding status in healthy patients, during critical illness there might be other factors, such as inflammation and nutrition status, that might contribute to the changes observed in ghrelin/PYY profiles.

Oral lactate slows gastric emptying and suppresses appetite in young males.

BACKGROUND: Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. METHODS: Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. RESULTS: Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p < 0.001) with no detectable difference between interventions (p = 0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p = 0.02) and elevated glucagon like peptide-1 (GLP-1, p = 0.045), insulin (p < 0.001), and glucagon (p < 0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p < 0.001), increased the feeling of being "full" (p = 0.008) and lowered the "anticipated future food intake" (p = 0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. CONCLUSION: Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. CLINICAL TRIAL REGISTRY NUMBER: NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.

Ghrelin, leptin and high-molecular-weight adiponectin in relation to depressive symptoms in older adults: Results from the Longitudinal Aging Study Amsterdam.

BACKGROUND: Ghrelin, leptin and high-molecular-weight (HMW) adiponectin have been linked to depression in middle-aged adults. Pathophysiological mechanisms of depression change as age progresses and it is unclear whether the same associations exist in older adults. METHODS: We analyzed the associations between ghrelin, leptin and HMW adiponectin and depressive symptoms (Center for Epidemiologic Studies Depression (CES-D) score ≥ 16) in a community-dwelling cohort of 898 participants in a multivariable logistic regression analysis at baseline and after three years of follow-up, were applicable stratified by sex, age and waist-hip-ratio (WHR). RESULTS: At baseline no significant associations were found. After three years of follow-up ghrelin was associated with higher odds for depressive symptoms (fully adjusted continuous analysis OR 2.27, 95% CI 1.42 - 3.61). There was effect modification for age and WHR, with significant associations in participants younger than 69.7 years (median) and with a WHR below 0.9554 (mean). In the sex-stratified analysis for leptin we found significant associations in men (fully adjusted continuous analysis OR 1.07, 95% CI 1.02 - 1.12). For HMW adiponectin there were no significant associations in the multivariable analysis. LIMITATIONS: As our cohort consisted of relatively healthy participants with intact cognitive function, selection bias may have contributed to lack of significant baseline associations. CONCLUSIONS: Our results show significant associations between ghrelin and - for men only - leptin and depressive symptoms after three years of follow up. This may provide a new therapeutic window for treatment of depressive symptoms in older adults, as both ghrelin and leptin are positively influenced by weight loss.

Impact of isoenergetic intake of irregular meal patterns on thermogenesis, glucose metabolism, and appetite: a randomized controlled trial.

BACKGROUND: Evidence is emerging that interdaily meal pattern variability potentially affects response such as thermic effect of food (TEF), macronutrient metabolism, and appetite. OBJECTIVES: To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile, and appetite regulation in women who are overweight or with obesity and confirmed insulin resistance. DESIGN: In a randomized crossover trial, 9 women [mean ± SD BMI (in kg/m2): 33.3 ± 3.1] with confirmed insulin resistance consumed a regular (14 d; 6 meals/d) and an irregular (14 d; 3-9 meals/d) meal pattern separated by a 14-d washout interval. Identical foods were provided during the interventions, and at the start and end of each meal pattern, participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for 3 h after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention. RESULTS: TEF (over 3 h) was significantly lower postirregular intervention compared with postregular (97.7 ± 19.2 kJ*3 h in postregular visit and 76.7 ± 35.2 kJ*3 h in postirregular visit, paired t test, P = 0.048). Differences in HOMA-IR between the 2 interventions (3.3 ± 1.7 and 3.6 ± 1.6 in postregular and postirregular meal pattern, respectively) were not significant. Net incremental AUC for GLP-1 concentrations (over 3 h) for the postregular meal pattern were higher (864.9 ± 456.1 pmol/L*3 h) than the postirregular meal pattern (487.6 ± 271.7 pmol/L*3 h, paired t test, P = 0.005). CONCLUSIONS: Following a 14-d period of an irregular meal pattern, TEF was significantly less than following a regular meal pattern, potentially compromising weight management if sustained long term. This study was registered at www.clinicaltrials.gov as NCT02582606.

Temporal changes and prognostic value of plasma ghrelin level in patients with acute heart failure: a prospective study.

BACKGROUND: Plasma ghrelin levels can be elevated in patients with acute heart failure (AHF). This study aimed to analyze the temporal changes and prognostic value of ghrelin levels in patients with AHF. METHODS: This prospective study included patients with AHF at the Cardiology Department, Weifang People's Hospital (May 2018-October 2019), and age- and sex-matched healthy controls. Plasma ghrelin levels were measured. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate whether ghrelin levels could predict major cardiac adverse events (MACEs) during a 1-year follow-up. RESULTS: Finally, 92 patients with AHF and 50 healthy controls were enrolled. Ghrelin levels were higher in patients with AHF at 1, 3, 12, and 24 h compared with controls (all P < 0.01). Ghrelin levels in the AHF group were higher at 3 and 12 h than at 1 and 24 h (P < 0.001). Ghrelin level at 3 h in patients with AHF was negatively correlated with the left ventricular end-diastolic diameter and left ventricular ejection fraction (both P < 0.05). MACEs occurred in 48 patients with AHF. Ghrelin levels were higher in the MACE group than in the non-MACE group at 1 (P = 0.011) and 3 h (P = 0.034). Multivariable regression showed that ghrelin level at 3 h was independently associated with MACEs [OR = 0.629, 95% confidence interval (CI): 0.515-0.742, P = 0.010], but the area under the ROC curve was only 0.629 (95% CI 0.515-0.742). CONCLUSIONS: Plasma ghrelin levels are elevated in AHF and patients with MACEs during follow-up.