Plasma Ghrelin Concentrations Research Articles

No Effect of High Eating Frequency Compared with Low Eating Frequency on Appetite and Inflammation Biomarkers: Results from a Randomized Crossover Clinical Trial

BackgroundEating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health. ObjectivesWe sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults. MethodsData are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined. ResultsAmong the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m2, and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: −0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers. ConclusionsNo differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health.This trial was registered at clinicaltrials.gov as NCT02392897.

Japanese Traditional Herbal Medicine, Rikkunshito, Partially Suppresses Inflammatory Responses in Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion (I/R) injury can cause additional damage to an ischemic myocardium, even after successful reperfusion therapy. Inflammation is a mechanism that exacerbates myocardial damage after I/R injury. Rikkunshito(RKT) is a traditional Japanese herbal medicine widely used to treat gastrointestinal symptoms. It attenuates inflammation and fibrosis in some diseases of the heart; however, it remains unclear whether RKT exerts cardioprotective effects against myocardial I/R injury. To elucidate this, we evaluated the effects of RKT pre-treatment by oral administration on the myocardium in a mouse model of in vivo I/R injury. Mice were randomly assigned to a group receiving distilled water (DW) or one receiving RKT (1000 mg/kg/day) for 14 days orally. For each of the RKT and DW groups, a sham group, an I/R 2 h group, and an I/R 24 h group were created. On day 15, myocardial I/R surgery was performed. The left anterior descending coronary artery (LAD) was ligated for 30 min, and reperfusion time was set at 2 h or 24 h. The myocardial infarct size (IS) was measured after 2 h of reperfusion, and cardiac cytokine mRNA expression levels were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR) after 2 h and 24 h of reperfusion. RKT pre-treatment significantly suppressed the cardiac mRNA expression level of interleukin-1β in the RKT-I/R 2 h group compared to the DW-I/R 2 h group (P < 0.05). Additionally, RKT significantly suppressed the mRNA expression levels of transforming growth factor-β compared to DW; the same result was obtained for the expression levels of interleukin-6. However, RKT did not reduce the IS or mRNA expression levels of the cardiac congestive markers natriuretic peptide a(NPPA) and natriuretic peptide b (NPPB). In addition, RKT did not alter the plasma concentration of ghrelin and sirtuin 1 (Sirt1), which have been reported to be stimulated by RKT. This study showed that pre-treatment of RKT for myocardial I/R injury partially suppressed inflammation-related cytokines. However, further studies are needed on the effect of RKT on the reduction of myocardial infarction size.

Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.

The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations. We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB). Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: -11.16; 95% CI: -18.52, -3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner. LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans. The study was retrospectively registered in clinicaltrials.gov (April 2023). gov Identifier: NCT05815641.

Plasma concentration of leptin is related to food addiction in gambling disorder: Clinical and neuropsychological implications.

Data implicate overlaps in neurobiological pathways involved in appetite regulation and addictive disorders. Despite different neuroendocrine measures having been associated with both gambling disorder (GD) and food addiction (FA), how appetite-regulating hormones may relate to the co-occurrence of both entities remain incompletely understood. To compare plasma concentrations of ghrelin, leptin, adiponectin, and liver-expressed antimicrobial peptide 2 (LEAP-2) between patients with GD, with and without FA, and to explore the association between circulating hormonal concentrations and neuropsychological and clinical features in individuals with GD and FA. The sample included 297 patients diagnosed with GD (93.6% males). None of the patients with GD had lifetime diagnosis of an eating disorder. FA was evaluated with the Yale Food Addiction Scale 2.0. All patients were assessed through a semi-structured clinical interview and a psychometric battery including neuropsychological tasks. Blood samples to measure hormonal variables and anthropometric variables were also collected. From the total sample, FA was observed in23 participants (FA+) (7.7% of the sample, 87% males). Whencompared participants with and without FA, those with FA+ presented both higher body mass index (BMI) (p < 0.001) andleptin concentrations, after adjusting for BMI (p = 0.013). In patients with FA, leptin concentrations positively correlated with impulsivity, poorer cognitive flexibility, and poorer inhibitory control. Other endocrine measures did not differ between groups. The present study implicates leptin in co-occurring GD and FA. Among these patients, leptin concentration has been associated with clinical and neuropsychological features, such as impulsivity and cognitive performance in certain domains.

Momordica balsamina improves glucose handling in a diet-induced prediabetic rat model

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention.

Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study

BackgroundWeight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined. ObjectiveThis study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings. MethodsThis was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m2; age: 47±1 y; 26 males) underwent an 8 wk low-energy diet, followed by 4 wk of refeeding and weight stabilization. The RMR, respiratory quotient (RQ), body composition, plasma concentrations of ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, insulin, and appetite ratings in the fasting and postprandial states were measured at baseline, Wk9 and 13. Metabolic adaptation was defined as significantly lower when measured versus the predicted RMR (pRMR) (from own regression model using baseline data). ResultsA 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ. ConclusionA larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.

The role of dysregulated ghrelin/LEAP-2 balance in anorexia nervosa

LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p= 0.043). After 6months follow-up, patients with unstable weight gain (n= 17) had significantly decreased LEAP-2 concentrations after refeeding (p= 0.044), in contrast to patients with stable weight gain (n= 12). We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN, in contrast to what is physiologically expected when coping with food restriction.

Development of pancreatic islet cells in the extrahepatic bile ducts of rats with experimentally-induced metabolic syndrome

Context There is data about the existence of some endocrine cells in the epithelial layer of the bile duct in humans and rats. Objective We evaluated Ghrelin-, Insulin-, Glucagon- and Somatostatin-positive cells in peribiliary glands, mast cells, and nerve fibres. Materials and methods Wistar rats were used for dietary manipulation with a 15% fructose solution for 12 weeks. Tissue samples were elaborated with immunohistochemistry for Insulin, Glucagon, Ghrelin, and Somatostatin. Glucose and lipid parameters were studied. Results In treated animals, Ghrelin+ and Insulin+ cells in perybiliary glands (PBGs) were significantly increased. In the male fructose group there was a significant increase of the homeostasis model assessment insulin resistance (HOMA-IR). Conclusions Stem/progenitor cells in extrahepatic bile tree (EHBT) could be a source of Insulin-producing cells in metabolic syndrome. Fructose treatment induces the increase of Ghrelin+ and Insulin+ cells in PBGs and the elevation of Insulin and Ghrelin plasma concentration.

Chronic food restriction in mice and increased systemic ghrelin induce preference for running wheel activity

ObjectivesIn eating disorders, particularly anorexia nervosa (AN), patients exhibit intense physical activity which is inappropriate regarding food restriction and chronic undernutrition, and exacerbates weight loss and energy deprivation. Rodent models of food restriction exhibit increased running wheel activity in the food anticipation period, also known as Food Anticipatory Activity (FAA). FAA probably has various physiological and/or neurobiological origins. Plasma concentrations of the orexigenic hormone ghrelin are, for example, increased during FAA. We hypothesize that the drive for physical activity in chronic food restriction is triggered by metabolic factors but also relies on motivational aspects that we aim to decipher in this study. MethodsYoung female C57Bl6/J mice were exposed to a paradigm based on a progressive 50% quantitative food restriction alone (FR) or associated with running wheel activity (Food Restriction Wheel: FRW) in their home-cage during 15 days. We measured preference for running wheel in a three-chamber apparatus in which animals could choose to explore either a known running wheel or a novel object. Testing took place either during resting or during FAA. We calculated the time spent in each compartment and the activity in running wheels. After progressive refeeding over 10 days, mice were tested again when refed. Plasma levels of both ghrelin isoforms were measured with selective immunoassays. ResultsWhen tested during FAA period, food restricted mice displayed increased preference for the running wheel compared to ad libitum fed controls. Both FR and FRW mice exhibited increased running time and distance in the wheel and running distance was correlated with ghrelin levels. Similar preference and behavior were found when testing took place during the resting period. Animals housed without an active wheel also exhibited active running. Progressive refeeding resulted in body weight restoration, a decrease in FAA and completely abolished preference for the running wheel. Refed animals displayed similar behavior as ad libitum fed controls. ConclusionsThese data provide evidence that food restriction-induced physical activity is closely correlated with metabolic adaptations to nutritional status implicating ghrelin in the quantity of physical activity.

The role of dysregulated ghrelin/LEAP-2 balance in eating disorder: a translational study in anorexia nervosa

IntroductionAnorexia nervosa (AN) is a complex psychiatric disorder characterized by a persistant decrease in food intake leading to dramatic weight loss and energy deficit. The ghrelin system is a key regulator of appetite and food intake across species. LEAP-2, a recently discovered ghrelin antagonist, appears to be up-regulated in obesity and opposes to the orexigenic drive of ghrelin. The evolution of LEAP-2 levels could be an interesting insight to reflect the regulation of appetite in eating disorders such as anorexia nervosa (AN).ObjectivesWe tested this hypothesis and here provide the first study exploring the ghrelin and LEAP-2 regulation in long-term food restriction followed by refeeding in both mice and patients suffering from AN.MethodsUsing a translational strategy, we compared the regulation of ghrelin and LEAP-2 concentrations in blood during food restriction and after refeeding i/ in female mice exposed to a 14 days protocol combining quantitative food restriction and running wheel activity followed by 10 days of progressive refeeding; ii/ in an ongoing longitudinal study of patients with AN evaluated before and after refeeding (n=30) as well as 6 months after hospital discharge to evaluate if the weight gain was stable (n=7) or unstable (n=10). Plasma concentrations of ghrelin and LEAP-2 were measured with selective immunoassays.ResultsLong-term food restriction in mice was associated with increased ghrelin (p&lt;0.001) and decreased LEAP-2 concentrations (p=0.006) compared to ad libitum fed controls. Refeeding led to a decrease in ghrelin (p&lt;0.01) and increase in LEAP-2 concentrations (p&lt;0.01). Patients with AN displayed increased ghrelin levels (p&lt;0.01) but also higher LEAP-2 concentrations on admission than after refeeding (p=0.04). LEAP-2 decreased with refeeding. On 17 patients re-evaluated 6 months after discharge, patients with unstable weight gain exhibited a greater decrease of LEAP-2 concentrations during refeeding compared to patient with stable weight gain (p=0.02). Decreasing LEAP-2 concentrations was able to predict a negative outcome (i.e. unstable weight gain) in 80% of the cases.ConclusionsWe provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN as it is in the case of a physiological adaptation to food restriction. Results from an ongoing longitudinal study exploring remission in AN suggest that the evolution of LEAP-2 concentrations during refeeding is opposed to data from preclinical model and could give new insights on the outcome of weight gain in AN.Disclosure of InterestNone Declared

Ghrelin, not corticosterone, is associated with transitioning of phenotypic states in a migratory Galliform.

In both captive and free-living birds, the emergence of the migratory phenotype is signalled by rapid and marked increases in food intake and fuelling, as well as changes in amount of nocturnality or migratory restlessness. The metabolic hormone corticosterone and, as more recently suggested, the gut-derived hormone ghrelin have been suggested to play a role in mediating such phenomenal phenotypic flexibility given that they both regulate fuel metabolism and locomotion across vertebrate taxa. Here, using the Common quail (Coturnix coturnix) as our study species, we induced autumn migration followed by a non-migratory wintering phase through controlled changes in daylight. We thus compared plasma corticosterone and ghrelin concentrations between the two sampling phases and assessed whether these hormones might reflect the migratory state. While we found no differences in plasma corticosterone between the two sampling phases and no link of this hormone with changes in body mass, levels of food intake or migratory restlessness, the migratory birds had substantially higher levels of plasma ghrelin relative to the non-migratory birds. Furthermore, while ghrelin did not correlate with the gain in body mass over the entire pre-migratory fuelling phase (over an average of nine weeks preceding blood sampling), plasma ghrelin did positively correlate with the gain in body mass observed during the final fattening stages (over an average of three weeks preceding blood sampling). Again, variation in plasma ghrelin also reflected the amount of body mass depleted over both the long- and short-time frame as birds returned to their non-migratory baseline - lower levels of plasma ghrelin consistently correlated with larger losses in body mass. Thus, while our data do not highlight a role of the hormone corticosterone in sustaining pre-migratory fattening as shown in other bird species, they do add evidence for a potential role of ghrelin in mediating migratory behaviour and further suggest that this hormone might be important in regulating the transitioning of migratory states, possibly by promoting fuel mobilisation and usage.

Short sleep duration is associated with high energy and total lipid intake in obese women: a pilot study

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.

Rice Endoplasmic Protein-Derived Peptides, Rice-Ghretropins A and B, Stimulate Ghrelin Release in MGN3-1 Cells and Increase Plasma Acylated Ghrelin and Food Intake in Mice.

In this study, we demonstrated that novel rice-derived bioactive peptides promote the secretion of ghrelin, an endogenous orexigenic hormone secreted from the stomach. The enzymatic digest of rice endosperm protein with subtilisin, a microorganism-derived enzyme, stimulated acylated ghrelin secretion in the ghrelin-releasing cell line MGN3-1 and increased food intake after oral administration in mice. By performing a comprehensive analysis based on structure-activity relationships, we selected candidate peptides from over 30,000 peptides in the rice digest. Among them, we found that QAFEPIRSV and TNPWHSPRQGSF, corresponding to the amino acid sequence of the rice endoplasmic proteins glutelin A1 or A2(52-60) and B1 or B2(31-42), respectively, stimulated acylated ghrelin release in MGN3-1 cells. We named them rice-ghretropins A and B. Pyroglutamate formation of rice-ghretropin A, [pyr1]-rice-ghretropin A, also promoted ghrelin secretion. Furthermore, oral administration of rice-ghretropins increased food intake, plasma ghrelin concentration, and small intestinal transit in mice. In addition, the subtilisin digest of the rice protein significantly increased food intake for 4 h in 9 month-old (control: 0.61 ± 0.049 g; digest: 0.83 ± 0.059 g) and 24 month-old mice (control: 0.52 ± 0.067 g; digest: 1.01 ± 0.064 g). In summary, we found that novel bioactive peptides, namely, rice-ghretropins, from the enzymatic digest of rice endosperm stimulated acylated ghrelin secretion and increased food intake. This is the first report of rice-derived exogenous bioactive peptides that increase acylated ghrelin secretion.

Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC)

BackgroundLow-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. ObjectivesTo evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000–2500 kcal/d) and with varying carbohydrate quality or quantity. MethodsWe performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on “acellular” carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), “cellular” carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. ResultsOf the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%−7%) and visceral fat volume (12%−17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: −16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: −39.6 pg/mL; 95% CI: −76, −3.3]). No significant between-group differences were seen in feelings of hunger. ConclusionsModestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3–0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.

Nut-enriched energy restricted diet has potential to decrease hunger in women at cardiometabolic risk: a randomized controlled trial (Brazilian Nuts Study)

Successful weight management represents a challenge to obesity control. Evidence suggests that nut consumption promotes a prolonged satiety response. Therefore, we hypothesize that nuts could be associated with greater weight loss in comparison to a control group, and we evaluate the acute and long-term effects of Brazilian nuts (BN: 15 g of Brazil nuts+30 g of cashew nuts) included in an energy-restricted intervention on food intake, appetite, and peptide hormones. We conducted an 8-week, randomized, open-label, controlled, parallel-arm clinical trial with 28 women at cardiometabolic risk who received an energy-restricted diet containing BN or an energy-restricted nut-free diet (control). At baseline and after 8 weeks of intervention, subjective postprandial appetite ratings were assessed using a visual analog scale (VAS) before and after consumption (0, 10, 60, 120, 180, and 240 minutes) of a 437-kcal nut-enriched (BN group) or nut-free (control) breakfast meal. Subsequently, an ad libitum lunch was served, and the participants completed another VAS at 280 minutes. Plasma concentrations of ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and leptin were measured at fasting and postprandially at 60, 120, and 240 minutes. Last, subsequent reported 24-hour energy intake was assessed in a free-living setting. BN consumption did not have acute effects on food intake, appetite, or peptide hormones. However, after an 8-week intervention, postprandial ghrelin (difference between post- and preintervention area under the curve) decreased in the BN group in comparison to the control (mean difference, 1978 pg/mL/min, 95% CI, 27-3929 pg/mL/min; P=.047) and therefore, an energy-restricted diet containing demonstrated potential to decrease hunger in cardiometabolic risk women.

Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis

Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane ‘Risk of bias tool for randomised trials’ (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18–20 °C) increased energy intake to a greater extent than neutral water (27–33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18–20 °C).

Plasma Concentrations of Gut Hormones Acyl Ghrelin and Peptide YY and Subsequent Risk of Colorectal Cancer and Molecular Tumor Subtypes.

The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.

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 &amp;lt; 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 &amp;lt; 0.01) for RFI and GHRL. The SNP rs423156356 at the GHSR1a gene was highly significant (p &amp;lt; 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.

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.

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&amp;lt; 0.05). In TN condition, LP tended to increase the average daily feed intake (ADFI) compared to NP (P&amp;lt; 0.1), while during HS, LP was not different from NP in terms of ADFI (P&amp;gt;0.05). In TN condition, LP had a higher thermal radiation than NP, but LP had less thermal radiation than NP during HS (P&amp;lt; 0.05). In support of ADFI data, LP had a greater ghrelin transcript in the duodenum than NP in TN condition (P&amp;lt; 0.05). However, during HS, LP tended to decrease the plasma ghrelin concentration compared with NP (P&amp;lt; 0.1). Unlike TN condition, LP had a decreased muscle sirtuin and cytochrome c oxidase transcript than NP during HS (P&amp;lt; 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.