Ghrelin Responses Research Articles

Ghrelin response to hedonic eating in underweight and short-term weight restored patients with anorexia nervosa

Recently, anorexia nervosa (AN) has been conceptualized as a reward-related disorder, and alterations in brain reward processes have been documented in both acute and recovered AN patients. However, the role of endogenous biochemical mediators, such as ghrelin, in the modulation of reward processes has been poorly investigated in this eating disorder. Hedonic eating, that is the consumption of food exclusively for pleasure and not to maintain energy homeostasis, is a useful paradigm to investigate the physiology of food-related reward. Therefore, we assessed the response of peripheral ghrelin to hedonic eating in 7 underweight and 7 recently weight-restored AN patients and compared it to that of previously studied healthy controls. We found that in satiated underweight patients with AN plasma ghrelin levels progressively decreased after the exposure and the consumption of both the favorite and unfavorite food whereas in satiated weight-restored AN patients and satiated healthy controls plasma ghrelin concentrations significantly increased after the exposure to the favorite food and after eating it, but decreased after the unfavorite food. These results suggest a derangement in the ghrelin modulation of food-related pleasurable and rewarding feelings, which might sustain the reduced motivation toward food intake of acute AN patients.

Gastrointestinal Hormones and Weight Loss Maintenance Following Roux-en-Y Gastric Bypass.

Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood. Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB. First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22). Second, we evaluated food intake (FI) following blockade of gut hormonal secretion in G-WL (n = 23) or P-WLM (n = 19) subjects. Finally, the impact of dietary-induced WL on the hormonal response in subjects with P-WLM (n = 14) was assessed. This study was undertaken in a tertiary hospital. In studies 1 and 3, the outcomes measures were the areas under the curve of gut hormones following a SMLM; in study 2, FI following subcutaneous injection of saline or octreotide were evaluated. P-WLM associated a blunted GLP-1 (P = .044) and PYY (P = .001) responses and lesser suppression of ghrelin (P = .032) following the SMLM challenge. On saline day, FI in the G-WL (393 ± 143 kcal) group was less than in the P-WLM (519 ± 143 Kcal; P = .014) group. Octreotide injection resulted in enlarged FI in both groups (G-WL: 579 ± 248 kcal, P = .014; P-WLM: 798 ± 284 Kcal, P = .036), but the difference in FI between groups remained (P < .001). In subjects with P-WLM, dietary-induced WL resulted in larger ghrelin suppression (P = .046), but no change in the GLP-1 or PYY responses. Our data show gastrointestinal hormones play a role in the control of FI following RYGB, but do not support that changes in GLP-1, PYY, or ghrelin play a major role as determinants of P-WLM after this type of surgery.

Impact of Duodenal-Jejunal Exclusion on Satiety Hormones.

Bariatric procedures that exclude the proximal small intestine lead to significant weight loss which is probably mediated by changes in hormones that alter appetite, such as peptide YY (PYY), ghrelin, cholecystokinin (CCK), and leptin. Here, the effect of the non-surgical duodenal-jejunal bypass liner (DJBL) on concentrations of hormones implicated in appetite control was investigated. A two-center prospective study was conducted between January and December 2010. Seventeen obese subjects with type 2 diabetes were treated with the DJBL for 24 weeks. Fasting concentrations of leptin and meal responses of plasma PYY, CCK, and ghrelin were determined prior to and after implantation of the DJBL. At baseline, subjects had an average body weight of 116.0 ± 5.8 kg. One week after implantation, subjects had lost 4.3 ± 0.6 kg (p < 0.01), which progressed to 12.7 ± 1.3 kg at week 24 (p < 0.01). Postprandial concentrations of PYY and ghrelin increased (baseline vs. week 1 vs. week 24 PYY: 2.6 ± 0.2 vs. 4.1 ± 0.4 vs. 4.1 ± 0.7 nmol/L/min and ghrelin: 7.8 ± 1.8 vs. 11.0 ± 1.8 vs. 10.6 ± 1.8 ng/mL/min, all p < 0.05). In parallel, the CCK response decreased (baseline vs. week 1 vs. week 24: 434 ± 51 vs. 229 ± 52 vs. 256 ± 51 pmol/L/min, p < 0.01). Fasting leptin concentrations also decreased (baseline vs. week 24: 98 ± 17 vs. 53 ± 10 ng/mL, p < 0.01). DJBL treatment induces weight loss paralleled by changes in concentrations of hormones involved in appetite control.

Metabolic Impairments Precede Changes in Hunger and Food Intake Following Short-Term Administration of Second-Generation Antipsychotics

The second-generation antipsychotics (SGAs) are associated with weight gain and an increased incidence of metabolic diseases. The metabolic impairments are assumed a consequence of increased body adiposity secondary to central nervous system-associated increases in food intake. We have previously reported that, independent of weight gain, 9 days of olanzapine administration to control subjects is associated with insulin resistance and increases in postprandial levels of insulin and glucagon-like peptide 1 to a mixed meal challenge. This current report describes previously unpublished data on the effects of the SGAs olanzapine and aripiprazole compared with placebo on detailed hunger and satiety responses over the 12-day inpatient evaluation as well as postprandial ghrelin and leptin responses prior to and following administration of the 2 SGAs. We found no changes in hunger, fullness, or in the orexigenic hormone ghrelin or satiety hormone leptin, consistent with our previous report indicating no change in weight during this study. The results indicate that the SGAs are associated with metabolic changes prior to changes in hunger, satiety, and food intake, and this temporal separation suggests that there are differential mechanisms mediating SGA-associated changes in metabolism and food intake.

MON-PP152: Satiety Index after the Intake of Two Breakfasts Based on Cow and Goat Dairy: Relationship with Ghrelin and GLP-1 Response

MON-PP152: Satiety Index after the Intake of Two Breakfasts Based on Cow and Goat Dairy: Relationship with Ghrelin and GLP-1 Response

Carbohydrate-rich breakfast attenuates glycaemic, insulinaemic and ghrelin response to ad libitum lunch relative to morning fasting in lean adults.

Breakfast omission is associated with obesity and CVD/diabetes, but the acute effects of extended morning fasting upon subsequent energy intake and metabolic/hormonal responses have received less attention. In a randomised cross-over design, thirty-five lean men (n 14) and women (n 21) extended their overnight fast or ingested a typical carbohydrate-rich breakfast in quantities relative to RMR (i.e. 1963 (sd 238) kJ), before an ad libitum lunch 3 h later. Blood samples were obtained hourly throughout the day until 3 h post-lunch, with subjective appetite measures assessed. Lunch intake was greater following extended fasting (640 (sd 1042) kJ, P< 0.01) but incompletely compensated for the omitted breakfast, with total intake lower than the breakfast trial (3887 (sd 1326) v. 5213 (sd 1590) kJ, P< 0.001). Systemic concentrations of peptide tyrosine-tyrosine and leptin were greater during the afternoon following breakfast (both P< 0.05) but neither acylated/total ghrelin concentrations were suppressed by the ad libitum lunch in the breakfast trial, remaining greater than the morning fasting trial throughout the afternoon (all P< 0.05). Insulin concentrations were greater during the afternoon in the morning fasting trial (all P< 0.01). There were no differences between trials in subjective appetite during the afternoon. In conclusion, morning fasting caused incomplete energy compensation at an ad libitum lunch. Breakfast increased some anorectic hormones during the afternoon but paradoxically abolished ghrelin suppression by the second meal. Extending morning fasting until lunch altered subsequent metabolic and hormonal responses but without greater appetite during the afternoon. The present study clarifies the impact of acute breakfast omission and adds novel insights into second-meal metabolism.

The influence of environmental temperature on appetite-related hormonal responses.

BackgroundAcute exercise in the heat has been shown to reduce appetite. However, the influence of exercise in the cold on appetite regulation remains unclear. The aim of this study was to compare exercise-induced appetite regulation under three different environmental temperatures.MethodsEleven male participants completed three experimental trials on the following separate days: exercise in the heat (36°C), exercise at neutral temperature (24°C), and exercise in the cold (12°C). The exercise trials consisted of pedaling exercises for 30 min at 65% of maximal oxygen uptake (VO2max). Blood samples were collected repeatedly to determine plasma ghrelin, peptide YY (PYY) and other hormonal concentrations. Subjective feelings of hunger and tympanic temperature were also monitored.ResultsTympanic temperature was significantly higher in the 36°C trial than that of the other two trials (P < 0.05). The subjective feelings of hunger in the 36°C and 24°C trials were significantly lower than those in the 12°C trial (P < 0.05). Plasma ghrelin concentration decreased significantly with exercise in all conditions (P < 0.05), and the responses were not significantly different among the three conditions. Plasma PYY concentration increased significantly after the exercise in the 24°C trial only (P < 0.05), with no significant difference among the three trials.ConclusionsThese results suggest that exposure to hot or cold temperatures during exercise did not affect exercise-induced plasma ghrelin and PYY responses. However, the exercise-induced reduction of subjective hunger was significantly attenuated in a cold environment.

A High–Glycemic Index, Low-Fiber Breakfast Affects the Postprandial Plasma Glucose, Insulin, and Ghrelin Responses of Patients with Type 2 Diabetes in a Randomized Clinical Trial1–3

Background: Meals with a low glycemic index (GI) and rich in fiber could be beneficial with regard to postprandial metabolic profile and satiety.Objective: The aim of this study was to investigate the effect of 4 breakfasts with a different GI and amount of fiber on postprandial plasma glucose, insulin, and appetite in patients with type 2 diabetes.Methods: This randomized 4-intervention crossover trial included 14 patients [7 men; ages 65.8 ± 5.2 y; glycated hemoglobin: 6.6 ± 0.9%; BMI (in kg/m2): 27.2 ± 3.1]. Dietary interventions were as follows: breakfasts with a high GI (60.4 ± 0.1%) and high fiber (6.0 ± 0.3 g) (HGI-HF), a high GI (60.9 ± 1.7%) and low fiber (2.5 ± 0.4 g) (HGI-LF), a low GI (37.7 ± 0.1%) and high fiber (6.2 ± 0.3 g) (LGI-HF), and a low GI (39.8 ± 1.3%) and low fiber (2.0 ± 0.1 g) (LGI-LF). Plasma glucose, insulin, and total ghrelin were evaluated postprandially (0–180 min). A visual analog scale was used to assess appetite. Data were analyzed by generalized estimating equations and post hoc least significant difference (LSD) tests. Data are reported as means ± SDs.Results: The area under the curve (AUC) [mean (95% CI); P for LSD tests] for plasma glucose (mmol/L × min) was higher after patients consumed the HGI-LF breakfast [9.62 (8.39, 10.84)] than after the LGI-HF breakfast [8.95 (7.71, 10.18)] (P ≤ 0.05). Insulin AUC (μIU/mL × min) after patients consumed the HGI-LF meal [65.72 (38.24, 93.19)] was higher than after the HGI-HF meal [57.24 (32.44, 82.04)] (P ≤ 0.05). The other observed difference was higher insulin AUC after the consumption of the LGI-LF breakfast [61.54 (36.61, 86.48)] compared with the AUC after the LGI-HF breakfast [54.16 (31.43, 76.88)] (P ≤ 0.05). Plasma ghrelin decreased in comparison with baseline only after patients consumed the LGI-HF and LGI-LF breakfasts (P ≤ 0.05). Subjective satiety did not differ between breakfasts.Conclusions: Plasma glucose, insulin, and ghrelin responses were least favorable when patients with type 2 diabetes consumed a breakfast with a high GI and low fiber, which suggests that reducing the GI or increasing the fiber content or both of breakfasts may be a useful strategy to improve the postprandial metabolic profile of these patients. This trial was registered at http://clinicaltrials.govas NCT01410292.

Meal-induced insulin sensitization is preserved after acute olanzapine administration in female Sprague-Dawley rats.

Olanzapine, an atypical antipsychotic, can acutely induce fasting insulin resistance, but we do not know whether it is able to modulate the meal-induced insulin sensitization (MIS). Two main experimental groups (control and olanzapine-treated) were created with two subgroups (fasted and re-fed) within each. After oral vehicle/olanzapine administration, the first meal size and duration and the total amount of consumed food was recorded in conscious rats. Then, under anaesthesia, the carotid artery and jugular vein was prepared and cannulated to obtain samples for blood glucose and hormone determination as well as for insulin/glucose infusion, respectively. Basal insulin sensitivity and MIS was determined by homeostasis model assessment (HOMA) calculation and by rapid insulin sensitivity test, respectively. In fasted animals, olanzapine increased blood glucose and plasma insulin and reduced basal insulin sensitivity, but it failed to modify other hormone levels. Postprandial leptin and glucose-dependent insulinotropic polypeptide (GIP) levels increased, and ghrelin level decreased significantly (p < 0.05) both in vehicle- and olanzapine-treated groups, but plasma insulin increased only in vehicle-treated animals. Furthermore, decrement in ghrelin level was attenuated in olanzapine-treated animals compared to controls. There was no significant change in the first meal size and duration or in the total amount of food consumed. Olanzapine had no effect on the MIS. We demonstrated that olanzapine can induce insulin resistance without weight gain in healthy rats. Furthermore, the MIS was preserved after acute olanzapine treatment. The blunted postprandial ghrelin and insulin response could contribute to the effect of olanzapine on feeding behaviour. Pharmacological induction of MIS may improve the olanzapine-induced insulin resistance.

Postprandial effects of polydextrose on satiety hormone responses and subjective feelings of appetite in obese participants.

BackgroundDietary fibers are associated with enhanced satiety. However, the mechanism of different dietary fibers contributing to satiety-related gastrointestinal (GI) peptide release, especially in an obese population, is still poorly understood. Polydextrose (PDX), a water-soluble glucose polymer, has demonstrated its ability to reduce energy intake at a subsequent meal, but its mechanism of action requires further research. Also, there is limited evidence on its capacity to regulate subjective feelings of appetite. This study examines the effects of PDX on postprandial secretion of satiety-related GI peptides, short chain fatty acids (SCFAs), lactic acid, and subjective appetite ratings in obese participants.Methods18 non-diabetic, obese participants (42.0 y, 33.6 kg/m2) consumed a high-fat meal (4293 kJ, 36% from fat) with or without PDX (15 g) in an acute, multicenter, randomized, double-blind, placebo-controlled and crossover trial. Postprandial plasma concentrations of satiety-related peptides, namely ghrelin, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), as well as SCFAs and lactic acid were assessed. GI peptide, SCFA and lactate concentrations were then modeled using a linear mixed-effects model.The subjective feelings of hunger, satisfaction, and desire to eat were evaluated using visual analogue scales (VAS), which were analyzed as incremental areas under the curve (iAUC) during the satiation and satiety periods.ResultsWe found that PDX supplementation increased plasma GLP-1 levels more than the placebo treatment (P = 0.02). In the whole group, GLP-1 concentrations found in participants older than 40 years old were significantly lower (P = 0.01) as compared to those aged 40 years or less. There were no statistically significant differences in postprandial ghrelin, CCK, or PYY responses. The lactic acid concentrations were significantly (P = 0.01) decreased in the PDX group, while no significant changes in SCFAs were found. PDX reduced iAUC for hunger by 40% (P = 0.03) and marginally increased satisfaction by 22.5% (P = 0.08) during the post-meal satiety period.ConclusionPolydextrose increased the postprandial secretion of the satiety hormone GLP-1 and reduced hunger after a high-fat meal. PDX also reduced the elevated postprandial lactic acid levels in plasma. Therefore, PDX may offer an additional means to regulate inter-meal satiety and improve postprandial metabolism in obese participants.

NUTRALYS® pea protein: characterization of in vitro gastric digestion and in vivo gastrointestinal peptide responses relevant to satiety

BackgroundPea protein (from Pisum sativum) is under consideration as a sustainable, satiety-inducing food ingredient.ObjectiveIn the current study, pea-protein-induced physiological signals relevant to satiety were characterized in vitro via gastric digestion kinetics and in vivo by monitoring post-meal gastrointestinal hormonal responses in rats. DesignUnder in vitro simulated gastric conditions, the digestion of NUTRALYS® pea protein was compared to that of two dairy proteins, slow-digestible casein and fast-digestible whey. In vivo, blood glucose and gastrointestinal hormonal (insulin, ghrelin, cholecystokinin [CCK], glucagon-like peptide 1 [GLP-1], and peptide YY [PYY]) responses were monitored in nine male Wistar rats following isocaloric (11 kcal) meals containing 35 energy% of either NUTRALYS® pea protein, whey protein, or carbohydrate (non-protein).ResultsIn vitro, pea protein transiently aggregated into particles, whereas casein formed a more enduring protein network and whey protein remained dissolved. Pea-protein particle size ranged from 50 to 500 µm, well below the 2 mm threshold for gastric retention in humans. In vivo, pea-protein and whey-protein meals induced comparable responses for CCK, GLP-1, and PYY, that is, the anorexigenic hormones. Pea protein induced weaker initial, but equal 3-h integrated ghrelin and insulin responses than whey protein, possibly due to the slower gastric breakdown of pea protein observed in vitro. Two hours after meals, CCK levels were more elevated in the case of protein meals compared to that of non-protein meals.ConclusionsThese results indicate that 1) pea protein transiently aggregates in the stomach and has an intermediately fast intestinal bioavailability in between that of whey and casein; 2) pea-protein- and dairy-protein-containing meals were comparably efficacious in triggering gastrointestinal satiety signals.

Adipocytokine and ghrelin responses to acute exercise and sport training in children during growth and maturation.

Physical exercise is known to regulate energy balance. Important to this regulatory system is the existence of several peptides that communicate the status of body energy stores to the brain and are related to the body fatness including leptin, adiponectin and ghrelin. These hormones assist in regulating energy balance as well as somatic and pubertal growth in children. It appears that rather few studies have investigated the responses of leptin, adiponectin and ghrelin to acute exercise and these studies have demonstrated no changes in these peptides as a result of exercise. Leptin levels are decreased and may remain unchanged advancing from prepuberty to pubertal maturation in young male and female athletes. A limited number of studies indicate that adiponectin levels are not different between prepubertal and pubertal athletes and untrained controls. However, in certain circumstances circulating adiponectin could be increased in young athletes after onset of puberty as a result of heavily increased energy expenditure. Ghrelin levels are elevated in young sportsmen. However, pubertal onset decreases ghrelin levels in boys and girls even in the presence of chronically elevated energy expenditure as seen in young athletes. Ghrelin may also be used as an indicator of energy imbalance across the menstrual cycle in adolescent athletes. There are no studies with high-molecular-weight adiponectin and only very few studies with acylated ghrelin responses to acute exercise and chronic training have been performed in young athletes. Since these forms of adiponectin and ghrelin have been thought to be bioactive forms, further studies with these specific forms of adiponectin and ghrelin are needed. In conclusion, further studies should be conducted to investigate the response of these hormones to acute and chronic negative energy balance to better understand their role in regulating energy balance during growth and maturation in young athletes.

Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats.

SummaryThe autonomic nervous system (ANS) conveys neuronal input from the brain to the stomach. We investigated mechanisms through which urocortin 1 (UCN1) injected intracerebroventricularly (ICV, 300 pmol/rat) inhibits circulating ghrelin in rats. This was achieved by assessing (1) the induction of c-fos gene expression as a marker of neuronal activation in specific hypothalamic and caudal brainstem regulating ANS; (2) the influence of vagotomy and pharmacological blockade of central and peripheral α- and β-adrenergic receptor (AR) on ICV UCN1 -induced reduction of plasma ghrelin levels (determined by ELISA); and (3) the relevance of this pathway in the feeding response to a fast in rats. UCN1 increased c-fos mRNA expression in key brain sites influencing sympathetic activity namely the hypothalamic paraventricular and ventromedial nuclei, locus coeruleus, nucleus of the solitary tract, and rostral ventrolateral medulla, by 16-, 29-, 6-, 37-, and 13-fold, respectively. In contrast, the dorsal motor nucleus of the vagus had little c-fos mRNA expression and ICV UCN1 induced a similar reduction in acylated ghrelin in the sham-operated (31%) and vagotomized (41%) rats. An intraperitoneal (IP) injection of either a non-selective α- or selective α2-AR antagonist reduced, while a selective α2-AR agonist enhanced ICV UCN1-induced suppression of plasma acylated ghrelin levels. In addition, IP injection of a non-selective β- or selective β1-AR agonist blocked, and selective β1-AR antagonist augmented, the ghrelin response to ICV UCN1. The IP injections of a selective α1- or non-selective β or β2-AR antagonists, or any of the pretreatments given ICV had no effect. ICV UCN1 reduced the 2-h food intake in response to a fast by 80%, and this effect was partially prevented by a selective α2-AR antagonist. These data suggest that ICV UCN1 reduces plasma ghrelin mainly through the brain sympathetic component of the ANS and peripheral AR specifically α2-AR activation and inactivation of β1-AR. The α2-AR pathway contributes to the associated reduction in food intake.

Imbalance Between Postprandial Ghrelin and Insulin Responses to an Ad Libitum Meal in Obese Women With Polycystic Ovary Syndrome

Obese women with polycystic ovary syndrome (PCOS) may have impairment in the regulation of food intake associated with ghrelin and insulin. In order to compare postprandial ghrelin and insulin responses to an ad libitum meal, we assessed 30 obese women with PCOS and 23 obese women without PCOS (control group). Blood samples were taken under fasting conditions, preprandially, and 15, 45, 75, and 135 minutes after the beginning of an ad libitum meal and ghrelin and insulin concentrations were analyzed. Insulin resistance (IR) was classified using basal insulin, quantitative insulin sensitivity check index, and homeostasis model assessment index. Mean ad libitum food intake was similar between the groups (468 ± 150 vs 444 ± 165 g, P = .60). The IR was found in 56.6% in PCOS group compared with 30.4% in the control group (P < .01). The postprandial ghrelin response was similar in both the groups but the insulin area under the curve (AUC) tend to be greater in the PCOS group (12807 ± 8149.4 vs 8654.4 ± 7232.3 μIU/mL/min; P = .057). The ghrelin AUC was negatively correlated with the insulin AUC (r = -.5138; P = .01) only in the control group. The imbalance in the feedback mechanisms between insulin and ghrelin, present in obese women, especially those with IR, may affect food intake throughout the day and that could be a mechanism for the development of obesity in PCOS.

Taste matters – effects of bypassing oral stimulation on hormone and appetite responses

The interaction between oral and gastric signals is an important part of food intake regulation. Previous studies suggest that bypassing oral stimulation diminishes the suppression of hunger and increases gastric emptying rate. However, the role of appetite hormones, like cholecystokinin-8 and ghrelin, in this process is still unclear. Our objective was to determine the contributions of gastric and oral stimulation to subsequent appetite and hormone responses and their effect on ad libitum intake. Fourteen healthy male subjects (age 24.6±3.8y, BMI 22.3±1.6kg/m2) completed a randomized, single-blinded, cross-over experiment with 3 treatment-sessions: 1) Stomach distention: naso-gastric infusion of 500mL/0kJ water, 2) Stomach distention with caloric content: naso-gastric infusion of 500mL/1770kJ chocolate milk, and 3) Stomach distention with caloric content and oral exposure: oral administration of 500mL/1770kJ chocolate milk. Changes in appetite ratings and plasma glucose, insulin, cholecystokinin-8, and active and total ghrelin concentrations were measured at fixed time-points up to 30min after infusion or oral administration. Subsequently, subjects consumed an ad libitum buffet meal. Oral administration reduced appetite ratings more than both naso-gastric infusions (P<0.0001). Gastric infusion of a caloric load increased insulin and cholecystokinin-8 and decreased total ghrelin concentrations more than ingestion (all P<0.0001). No differences in active ghrelin response were observed between conditions. Ad libitum intake did not differ between oral and gastric administration of chocolate milk (P>0.05). Thus, gastric infusion of nutrients induces greater appetite hormone responses than ingestion does. These data provide novel and additional evidence that bypassing oral stimulation not only affects the appetite profile but also increases anorexigenic hormone responses, probably driven in part by faster gastric emptying. This confirms the idea that learned associations between sensory characteristics and associated metabolic consequences serve to adapt hormone responses to nutrient content. These findings underscore the importance of oral stimulation in the regulation of food intake.

Neonatal events, such as androgenization and postnatal overfeeding, modify the response to ghrelin.

It is currently accepted that ambient, non-genetic factors influence perinatal development and evoke structural and functional changes that may persist throughout life. Overfeeding and androgenization after birth are two of these key factors that could result in “metabolic imprinting” of neuronal circuits early in life and, thereby, increase the body weight homeostatic “set point”, stimulate appetite, and result in obesity. Our aim was to determine the influence of these obesogenic factors on the response to ghrelin. We observed the expected orexigenic effect of ghrelin regardless of the nutritional or hormonal manipulations to which the animals were subjected to at early postnatal development and this effect remained intact at later stages of development. In fact, ghrelin responses increased significantly when the animals were subjected to one of the two manipulations, but not when both were combined. An increased response to ghrelin could explain the obese phenotype displayed by individuals with modified perinatal environment.

The Effect of Environmental Temperature During Exercise on Exercise-Induced Ghrelin Response

The Effect of Environmental Temperature During Exercise on Exercise-Induced Ghrelin Response

The neural signature of satiation is associated with ghrelin response and triglyceride metabolism

Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination.

Carbohydrate‐rich snacks influence plasma glucose, insulin and ghrelin responses in overweight adults (1039.5)

The effects of a whole food (dried plums; DP) or refined (low‐fat muffins; LFM) snack on satiety and insulin responses following consumption were assessed before and after a snack intervention trial. Forty overweight men and women (age: 36.5 + 11.4, BMI: 32.8 + 7.1 kg/m2) were randomly assigned to consume isocaloric, macronutrient‐matched 100 kcal snacks twice per day of DP or LFM for 8‐weeks. At baseline and 8 weeks, fasted subjects consumed 238 kcal of their randomly assigned food, and blood samples were collected at baseline, 15, 30, 45, 60, 90, and 120 min following intake. Insulin was lower (p蠄0.05) and an earlier peak was observed in DP versus LFM at baseline and 8 weeks. Both groups exhibited lower plasma glucose during the acute response testing after 8 weeks, but glucose peaked earlier in DP than LFM. There were no significant differences in ghrelin concentration over time in either group. These results support the concept that consuming a whole food snack such as dried plums enhances insulin sensitivity as compared to an isocaloric refined snack food, as evidenced by lower insulin concentrations and an earlier peak in insulin and glucose in DP compared to LFM.Grant Funding Source: Supported by the California Dried Plum Board

Unstimulated and glucose-stimulated ghrelin in depressed patients and controls

The neuropeptide ghrelin stimulates hunger and weight gain. Ghrelin actions have been associated with depression in a number of preclinical and clinical studies, although some studies comparing basal peripheral ghrelin levels between depressed patients and controls found no differences between the groups. Twenty patients with a melancholic depressive episode and 15 controls received a 75 g glucose load and ghrelin levels were measured at 0, 30, 60 and 90 min after the beginning of the test. The patients were then either treated with mirtazapine (n=10) or venlafaxine (n=10) and underwent the same procedure (glucose load and ghrelin assessment) after four weeks of treatment. Basal ghrelin concentrations did not differ between patients and controls, although the ghrelin responses following the glucose load were lower in patients and differed significantly to the controls' responses. After treatment, the patients' ghrelin responses to the glucose load increased by trend and approximated those in the control group. Ghrelin is involved in appetite-regulating pathways during depression. For the first time we show that a functional test procedure using a standardised glucose load is more suitable than the assessment of basal peripheral ghrelin levels to detect differences between diagnostic groups.