The effect of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus.

AIMS: To determine the effects of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus. METHODS: Two separate studies, each involving eight adults with uncomplicated Type 1 diabetes, were performed: one in the fasted state (A) and the other after a nutrient preload (B). In both studies, perceptions of appetite (hunger and fullness) and food intake at a buffet meal were evaluated during euglycaemia (blood glucose, approximately 6 mmol/l) and hyperglycaemia (blood glucose, approximately 14 mmol/l). Both experiments were randomized and single-blind. In study A, appetite was assessed in the fasted state for 90 min before the buffet meal. In study B, a nutrient 'preload' of Ensure and milk containing 13C-octanoic acid was consumed 90 min before the meal. Gastric emptying of the preload was quantified with a radioisotopic breath test technique. RESULTS: There was no significant difference in plasma insulin concentrations between euglycaemia and hyperglycaemia in either study. In study A, there were no differences in hunger, fullness or energy intake between the two treatment days. In study B, subjects were slightly less hungry between the preload and buffet meal during hyperglycaemia than euglycaemia (P = 0.04), and tended to have slower gastric emptying during hyperglycaemia (emptying coefficient, 3.89 +/- 0.16 vs. 3.57 +/- 0.21; P = 0.052), but there was no difference in food intake between hyperglycaemia and euglycaemia. CONCLUSIONS: Acute hyperglycaemia suppresses hunger after a nutrient preload, but not in the fasted state, in patients with uncomplicated Type 1 diabetes. This effect is small and not associated with changes in food intake.     

Role of the duodenum and macronutrient type in ghrelin regulation

The orexigenic hormone ghrelin is implicated in preprandial hunger and meal initiation in part because circulating levels increase before meals and decrease after food intake. The mechanisms underlying postprandial ghrelin suppression are unknown. Although most ghrelin is produced by the stomach, we have shown that neither gastric nutrients nor gastric distension affect ghrelin levels. We hypothesized that the nutrient-sensing mechanism regulating ghrelin is in the duodenum, the second richest source of ghrelin. To test whether duodenal nutrient exposure is required for ghrelin suppression, we infused nutrients into either the proximal duodenum or proximal jejunum in rats bearing chronic intestinal cannulas. At 0, 30, 60, 90, 120, 180, 240, and 300 min after infusions, blood was sampled via jugular-vein catheters for ghrelin, insulin, and glucose measurements. To elucidate further the mechanisms governing nutrient-related ghrelin suppression, we also assessed the ghrelin responses to isocaloric (3 kcal) infusions of glucose, amino acids, or lipids delivered into the stomach or small intestine of chronically catheterized rats. Regardless of macronutrient type, the depth and duration of ghrelin suppression were equivalent after gastric, duodenal, and jejunal infusions. Glucose and amino acids suppressed ghrelin more rapidly and strongly (by approximately 70%) than did lipids (by approximately 50%). Because jejunal nutrient infusions suppressed ghrelin levels as well as either gastric or duodenal infusions, we conclude that the inhibitory signals mediating postprandial ghrelin suppression are not derived discretely from either the stomach or duodenum. The relatively weak suppression of ghrelin by lipids compared with glucose or amino acids could represent one mechanism promoting high-fat dietary weight gain.     

Appetite hormones and energy intake in obese men after consumption of fructose, glucose and whey protein beverages

OBJECTIVE: To investigate appetite responses over 4 h to fructose beverages in obese men, relative to glucose and whey protein. Second, to investigate the effect of combining whey and fructose on postprandial appetite hormones. DESIGN: Randomized, double-blind crossover study of four beverages (1.1 MJ) containing 50 g of whey, fructose, glucose or 25 g whey+25 g fructose. Blood samples and appetite ratings were collected for 4 h then a buffet meal was offered. SUBJECTS: Twenty-eight obese men (age: 57.0+/-1.6 years, body mass index: 32.5+/-0.6 kg/m(2)). MEASUREMENTS: Plasma ghrelin (total), glucagon-like peptide-1 (GLP-1 7-36), cholecystokinin-8, glucose, insulin and appetite ratings were assessed at baseline and 30, 45, 60, 90, 120, 180, 240 min after beverages, followed by measurement of ad libitum energy intake. RESULTS: Fructose produced lower glycaemia and insulinaemia compared to the glucose treatment (P<0.0001); whereas postprandial ghrelin, GLP-1 and cholecystokinin responses were similar after both treatments. Whey protein produced a prolonged (2-4 h) suppression of ghrelin (P=0.001) and elevation of GLP-1 (P=0.002) and cholecystokinin (P=0.003) that were reduced when combined with fructose, while glucose and insulin responses were similar. Energy intake after 4 h was independent of beverage type (glucose 4.7+/-0.2 MJ; fructose 4.9+/-0.3 MJ; whey 4.6+/-0.3 MJ; whey/fructose 4.8+/-0.3 MJ; P>0.05). CONCLUSION: In obese men, fructose- and glucose-based beverages had similar effects on appetite and associated regulatory hormones, independent of the differing glycaemic and insulinaemic responses. The contrasting profile of plasma ghrelin, GLP-1 and cholecystokinin after whey protein consumption did not impact on ad libitum intake 4 h later and was attenuated when 50% of whey was replaced with fructose.     

Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy

CONTEXT: Patients with gastric or esophageal surgery and transection of the vagus nerve may suffer from appetite and weight loss but without dysphagia or mechanical obstruction to eating. The gastric hormone ghrelin stimulates food intake and GH release in rodents and man. However, rodents with vagotomy are not sensitive to the feeding effects of ghrelin. OBJECTIVE: The objective of the study was to determine whether humans with vagotomy are sensitive to ghrelin. STUDY DESIGN: The design was a double-blind, randomized, placebo-controlled trial. SETTING: This was a hospital-based study. PATIENTS: Six men and one woman who all had a previous complete truncal vagotomy with lower esophageal or gastric surgery entered and completed the study. INTERVENTION: Each patient received 120-min infusions of saline, 1 pmol/kg.min ghrelin, and 5 pmol/kg.min ghrelin on 3 separate days. After 90 min, a buffet meal was served. MAIN OUTCOME MEASURE: Energy intake at the buffet meal was measured. RESULTS: Ghrelin-stimulated GH release in a dose-dependent manner was measured, confirming bioactivity. However, no change in energy intake was observed with either dose of ghrelin [energy intake (kilojoules): saline 2805 +/- 812; ghrelin 1 pmol/kg.min, 2486 +/- 767; ghrelin 5 pmol/kg.min, 2382 +/- 543; P = not significant]. CONCLUSIONS: Ghrelin is unlikely to be an effective appetite-stimulatory treatment for patients with vagotomy and esophageal or gastric surgery. Our results suggest that an intact vagus nerve may be required for exogenous ghrelin to increase appetite and food intake in man.     

Ghrelin secretion is modulated in a nutrient- and gender-specific manner

BACKGROUND: Ghrelin is a potent GH secretagogue that also plays an important role in appetite and weight regulation. Ghrelin increases hunger and food intake, and its levels decrease after a standard meal or glucose. OBJECTIVE: To examine the effects of standard oral glucose, lipid and protein loads on ghrelin levels, investigating the possibility that these responses may be modulated by several anthropometric and metabolic factors. SUBJECTS AND METHODS: There were 24 adult nondiabetic subjects (13 men/11 women; mean age 55.3 +/- 2.9 years, range 26-74 years). Each participant underwent one or more of the following nutrient loads: (i) a standard oral glucose (75 g) load (n = 18); (ii) an oral lipid load (40 g, with 24 g saturated fat; n = 13); (iii) an oral protein load (40 g; n = 11). RESULTS: Fasting ghrelin levels were negatively related to body mass index (BMI; r =-0.47; P = 0.02), waist circumference (r = -0.58; P = 0.0028), waist/hip ratio (r = -0.56; P = 0.0046), fasting insulin (r = -0.44, P = 0.03), and homeostasis model assessment insulin resistance index (HOMA-R; r = -0.43, P = 0.034). Glucose load induced a decrease in ghrelin levels (P < 0.0001), and this response was modulated by sex (P < 0.0001), in that levels were significantly higher in females. The presence of obesity affected ghrelin response to glucose (< 0.0217), in that log-transformed ghrelin levels started to increase back to baseline after its initial decline earlier in obese than in lean subjects. Ghrelin levels after a glucose load were lower over time in subjects with more pronounced insulin resistance (P < 0.0001). Similarly, ghrelin levels decreased significantly following the lipid meal (P = 0.035), and were modulated by HOMA-R (P = 0.027) and gender (P = 0.029). Protein did not affect ghrelin levels. CONCLUSIONS: This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.     

Insulin, unlike food intake, does not suppress ghrelin in human subjects

Food intake suppresses plasma levels of the gastric peptide ghrelin in humans. We hypothesize that the food intake- suppression of ghrelin could be secondary to the plasma glucose and insulin changes after a meal. The aim of this study was to compare the effect of the administration of a combined pulse of glucose and insulin to the effect of one meal on plasma ghrelin in human subjects. A secondary aim was to study the effect of an oral glucose load on ghrelin levels. Methods: Experiment 1 (n = 10) studied plasma glucose, insulin, leptin and ghrelin for 6 hours after a 790 kcal liquid meal. In Experiment 2 (n = 7), a subcutaneous pulse of insulin (Humalog 0.03U/kg) and an I.V. infusion of glucose were administered in order to mimic the plasma changes of glucose and insulin after a meal, and plasma ghrelin levels were monitored for 9 h. The OGTT data was used to study the effect of oral glucose on ghrelin. Results: A mixed liquid meal decreased basal serum ghrelin by 26% at 40 minutes (p = 0.009). A 75 gr oral glucose load suppresses ghrelin by 28% at 30 minutes. Contrary to the meal effect, the parenteral administration of insulin and glucose did not suppress serum ghrelin. Conclusion: Unlike food intake, the administration of insulin and glucose does not suppress ghrelin levels. These data suggest that the suppressive effect of food intake or oral glucose on serum ghrelin is unlikely mediated by the changes of plasma insulin and glucose observed after the ingestion.     

Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial

There is a pressing need for more effective appetite-stimulatory therapies for many patient groups including those with cancer. We have previously demonstrated that the gastric hormone ghrelin potently enhances appetite in healthy volunteers. Here, we performed an acute, randomized, placebo-controlled, cross-over clinical trial to determine whether ghrelin stimulates appetite in cancer patients with anorexia. Seven cancer patients who reported loss of appetite were recruited from oncology clinics at Charing Cross Hospital. The main outcome measures were energy intake from a buffet meal during ghrelin or saline infusion and meal appreciation as assessed by visual analog scale. A marked increase in energy intake (31 +/- 7%; P = 0.005) was observed with ghrelin infusion compared with saline control, and every patient ate more. The meal appreciation score was greater by 28 +/- 8% (P = 0.02) with ghrelin treatment. No side effects were observed. The stimulatory effects of ghrelin on food intake and meal appreciation seen in this preliminary study suggest that ghrelin could be an effective treatment for cancer anorexia and possibly for appetite loss in other patient groups.     

Antihyperglycaemic medication modifies factors of postprandial satiety in type 2 diabetes

Aim: Type 2 diabetes is characterized by hyperglycaemia, delayed gastric emptying and a blunted response of gut hormones during feeding that may modulate satiety. We hypothesized that it is associated with more hunger when treated by medication. Methods: We studied nine type 2 diabetic men (A1C: 6.7 ± 0.3%, waist circumference: 104 ± 4 cm) after an overnight fast, during 5 h in response to a 2.88 MJ breakfast, twice, in a crossover design, with or without antihyperglycaemic agents. Satiety ratings, thermic effect of meal, gastric emptying, plasma concentrations of gut peptides, leptin, insulin and substrates and intake from a subsequent buffet were determined. Results: With medication, fasting and postprandial plasma glucose levels were lower but area under the curve (AUC) did not vary vs. without medication. Gastric emptying was shortened, branched chain amino acids (BCAA) AUC and thermic effect were lower, and postprandial glucagon‐like peptide‐1 (GLP‐1) and peptide tyrosine tyrosine (PYY_3–36) were maintained at higher levels beyond 4 h. Correlations were significant between duration of diabetes and fasting ghrelin (r = 0.779, p = 0.013) and peak insulin (r = ?0.769, p = 0.016), 5‐h postmeal ghrelin and peak glucose (r = 0.822, p = 0.007), 5‐h glucose and GLP‐1 (r = ?0.788, p = 0.012), and 5‐h hunger scores and energy intake at buffet (r = 0.828, p = 0.006). Without medication, fullness scores correlated with BCAA levels. Visual analogue scale scores, ghrelin and leptin levels did not differ between studies. Conclusions: The decrease in factors associated with postprandial satiety with treatment is counterbalanced by higher GLP‐1 and PYY_3–36. Medication may normalize the link between perception of hunger and subsequent food intake.     

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

OBJECTIVE: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. DESIGN: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal). SUBJECTS: Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.9+/-3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7+/-5.8 kg/m(2)), 10 middle-aged non-obese (BMI 23.5+/-2.2 kg/m(2)) and 10 young non-obese (BMI 22.7+/-1.8 kg/m(2)). MEASUREMENTS: Ghrelin, glucose and insulin levels were analysed pre- and postprandially. RESULTS: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. CONCLUSION: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.     

Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake

CONTEXT: Although dietary protein produces higher acute satiety relative to carbohydrate, the influence of protein source and body mass index (BMI) has not been clearly described. OBJECTIVE: The objective of the study was to assess postprandial responses to different protein sources, compared with glucose, in males with normal and high BMI. DESIGN: This was a randomized, crossover study of four preloads followed by blood sampling (+15, 30, 45, 60, 90, 120, 180 min) and buffet meal. SETTING: The study was conducted at an outpatient clinic. PARTICIPANTS: The study population included 72 men, with a BMI range 20.6-39.9 kg/m(2). INTERVENTIONS: Interventions consisted of liquid preloads (1.1 MJ, 450 ml) containing 50 g whey, soy, gluten, or glucose. MAIN OUTCOME MEASURES: Fasting and postprandial plasma glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (n = 38), ad libitum energy intake, and appetite ratings were measured. RESULTS: Energy intake was 10% lower after all protein preloads, compared with the glucose treatment (P < 0.05), independent of BMI status and protein type. All protein loads prolonged the postprandial suppression of ghrelin (P < 0.01) and elevation of GLP-1 (P < 0.01) and cholecystokinin (P < 0.05). Fasting GLP-1 concentrations [overweight, 17.5 +/- 1.3; lean, 14.7 +/- 0.1 pg/ml (5.2 +/- 0.4 and 4.4 +/- 0.1 pmol/liter, respectively); P < 0.001] and postprandial responses (P = 0.038) were higher in overweight subjects. CONCLUSIONS: Whey, soy, and gluten similarly tend to reduce ad libitum food intake 3 h later in lean and overweight males relative to glucose. Postprandial ghrelin, GLP-1, insulin, and cholecystokinin may contribute to this higher satiety after protein consumption. GLP-1 concentrations are increased in overweight subjects, which may affect satiety responses in this group.     

Effects of age on proximal gastric motor and sensory function

BACKGROUND: Healthy aging is associated with a reduction in appetite and food intake, which may predispose to pathologic weight loss and malnutrition. Changes in intragastric mechanisms mediating satiation in the elderly have not been studied. The aim of this study was to evaluate the effects of aging on i) fasting gastric compliance and the perception of gastric distension, and ii) food intake and gastric accommodation to a meal. METHODS: Five healthy older (aged 68-73 years) and five healthy young (aged 22-27 years) men, matched for body mass index, were each studied on three occasions after an overnight fast. On one day ('barostat day'), isovolumetric and isobaric distensions of the proximal stomach were performed, and meal-induced changes in intrabag volume were measured with an electronic barostat. On another day ('tube-only day') subjects were intubated with a nasogastric tube without an intragastric bag before the meal. On the 3rd day (control day) subjects were given the meal without intubation. Energy intake from the buffet meal was quantified, and perceptions assessed using visual analogue questionnaires. RESULTS: During both isobaric and isovolumetric distensions the pressure-volume relationship did not differ significantly between older and young subjects. During gastric distensions perceptions of fullness (P < 0.01), abdominal discomfort (P < 0.05), and bloating (P < 0.05) were less in older than young subjects, whereas the perception of hunger (P < 0.05) was less in the young than in older subjects. There was no difference in energy intake (P = 0.44) between young and older subjects. Food intake was less on the barostat day (P < 0.01) and the tube-only day (P < 0.01) than on the control day in young subjects but was not affected by the different study conditions in the older subjects. After the meal the maximum intrabag volume occurred later in the older than in the young subjects (105 +/- 4 min versus 36 +/- 8 min; P < 0.05), and the intrabag volume change was greater (P = 0.05) in the older than the young subjects later in the postprandial period. CONCLUSIONS: Healthy aging is associated with decreased perception of gastric distension without any change in fasting gastric compliance and with reduced gastric tone late in the postprandial period when compared with the young. Control of food intake is less sensitive to external stimuli in older than in young subjects.     

Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men

CONTEXT: Dietary proteins appear to be more satiating than carbohydrate. The mechanism and effect of protein and carbohydrate type are unclear. OBJECTIVE: The objective of the study is to compare the acute effect of different proteins and carbohydrates on indicators of appetite and appetite regulatory hormones. DESIGN: This is a randomized cross-over study of four orally consumed preloads followed by blood sampling (+15, 30, 45, 60, 90, 120, 180 min), then a buffet meal. SETTING: The study was carried out in an outpatient clinic. PATIENTS AND OTHER PARTICIPANTS: Nineteen overweight (body mass index 32.1 +/- 0.9 kg/m(2)) men participated. INTERVENTIONS: Liquid preloads (1 MJ) contained whey (55 g), casein (55 g), lactose (56 g), or glucose (56 g). MAIN OUTCOME MEASURES: Plasma ghrelin, cholecystokinin (CCK), insulin, glucose and amino acids, gastric emptying rate (plasma paracetamol), appetite rating (visual analog scale), and ad libitum energy intake were the main outcome measures. RESULTS: Energy intake was 10 +/- 3% higher after the glucose preload compared with lactose and protein preloads (P < 0.05), which were predicted by ghrelin at 120 min (P < 0.05). CCK was 71 +/- 6% higher 90 min after the protein preloads compared with glucose and lactose (P < 0.05), which predicted appetite at 180 min (P < 0.05). There was a small increase in branched chain amino acids after the whey preload compared with casein (P < 0.01), but this was independent of appetite and energy intake. CONCLUSION: Acute appetite and energy intake are equally reduced after consumption of lactose, casein, or whey compared with glucose, which was consistent with differences in plasma ghrelin. Higher CCK responses after proteins correlated with satiety but did not affect energy intake.     

The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat

Circulating levels of ghrelin, a stomach peptide that promotes food intake, rise before and fall after meal. We aimed to investigate whether there is an independent contribution of the small bowel to the regulation of ghrelin and appetite. A duodenal-jejunal bypass (DJB) with preservation of normal gastric volume and exposure to nutrients was performed in 12-wk-old obese Zucker ZDF fa/fa rat. Food intake, weight gain, 48-h fasting, and 24-h refeeding levels of total and acylated ghrelin were measured. The DJB was challenged against gastric banding (GB), diet, and a sham operation in matched animals. Normal controls were age-matched Wistar rats, which underwent either DJB or a sham operation. The Zucker obese animals showed a paradoxical increase of acylated ghrelin levels after refeeding (+30% with respect to fasting levels; P = 0.001), an abnormality that was completely reversed only by the DJB (-30%; P = 0.01) but not after GB, diet, or sham operation. In obese rats, the DJB resulted in significantly less food intake and weight gain compared with both GB (P < 0.05) and sham operation (P < 0.01). In sharp contrast, the DJB did not alter food intake and weight gain in normal rats. The DJB does not physically restrict the flow of food but restores meal-induced suppression of acylated ghrelin and significantly reduces food intake in Zucker obese rats. These findings suggest an independent intestinal contribution to the regulation of the dynamic ghrelin response to eating and the possibility that defective signaling from the proximal bowel could be involved in the pathogenesis of obesity/hyperphagia.     

Thermodynamic effects of bile acids in the stomach

The surface thermodynamic effects of bile acids in the stomach were assessed in 48 subjects who had undergone gastric surgery for peptic ulcer disease and in 52 controls with medically healed ulcers. We derived values for surface tension of gastric mucosa from contact angle using a goniometer and measured the surface tension of gastric juice by the drop-weight method. Subjects with gastric surgery had higher median fasting bile acid concentrations than controls (1.2 vs. 0.1 mmol/L; P less than 0.0001), higher mean mucosal surface tension (51.9 vs. 47.9 mN/m; P less than 0.0001), and lower mean surface tension of gastric juice (43.2 vs. 51.7 mN/m; P less than 0.0001). Subjects who had had a Billroth II gastrectomy (n = 19) had higher bile acid concentrations (5.8 vs. 0.6 mmol/L; P less than 0.01), higher mucosal surface tension (53.7 vs. 50.3 mN/m; P less than 0.05), and lower gastric juice surface tension (41.3 vs. 47.1 mN/m; P less than 0.05) than those who had a vagotomy and drainage procedure (n = 17). Overall, intragastric bile acid concentration correlated directly with surface tension of gastric mucosa (r = 0.51, P less than 0.0001) and inversely with that of gastric juice (r = -0.60, P less than 0.0001). In conclusion, the interfacial energy barrier at the surface of the gastric mucosa is overcome in the presence of intragastric bile acids.     

Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics

Ghrelin is an acylated 28-amino-acid peptide that stimulates food intake, GH secretion, and gastric motility. Experimental studies have suggested that ghrelin plays roles in glucose homeostasis, atherosclerosis, and microangiopathy. We investigated possible involvement of ghrelin in micro- and macro-vascular diabetic complications and glycemic control in diabetic patients. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured in 108 and 61 Japanese diabetic patients, respectively. Plasma ghrelin concentrations were negatively correlated with body mass index (BMI) (r = -0.309, P = 0.002) or HbA(1c) (r = -0.264, P = 0.0065). Plasma ghrelin levels in patients with diabetic nephropathy who showed high serum creatinine levels (s-Cre) were significantly higher than those in patients who showed normal s-Cre (P<0.02). In patients with diabetic triopathy, plasma ghrelin concentrations were significantly lower than those in patients without diabetic complications (P<0.05). Stepwise multiple regression analyses revealed that s-Cre, BMI, and HbA(1c) were independently associated with plasma ghrelin levels. A postprandial decrease of ghrelin was observed in patients with normal CV(R-R) values or those with normal body weight, whereas it was not seen in obese patients or in patients with low CV (R-R) values. Suppression rates of ghrelin 30-60 min after a test meal in obese patients were significantly lower than those in normal-weight patients. These findings suggest that ghrelin secretion is suppressed by long-term hyperglycemia and that obesity influences the regulation of ghrelin secretion.     

Post-prandial decrease of circulating human ghrelin levels.

Ghrelin, an endogenous ligand of the GH secretagogue-receptor, has recently been shown to stimulate GH secretion and to have orexigenic and adipogenic effects in rodents, but little is known about its regulation and biological function in humans. Gastric motor function is under control of the central nervous system; however, the afferent and efferent loops of this feedback control mechanism remain to be elucidated. In the study presented here we investigated the effect of nutrient intake on circulating human ghrelin levels, and a possible association between ghrelin levels and gastric emptying. Ten healthy volunteers received a standard meal after an overnight fast. Food intake significantly decreased plasma ghrelin levels from 248.5 +/- 15.0 to 179.5 +/- 17.9 fmol/ml (120 min after meal, p=0.047). Gastric emptying half-time (non-invasive 13C-octanoic acid breath test) was correlated with fasting plasma ghrelin levels (r=0.74, p=0.0013). Ghrelin appears to be one possible candidate to provide feedback signaling between nutrient intake, gastric motor function and the central nervous system.     

Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers

BACKGROUND: The gastric hormone ghrelin appears a useful agent to stimulate food intake in people with anorexia of illness. The loss of ghrelin's acyl group renders it inactive, thus it has been thought that subcutaneous administration may be problematic. OBJECTIVE: To investigate whether human subjects are sensitive to the effects of ghrelin administered by single subcutaneous injection. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. SUBJECTS: Sixteen healthy lean volunteers (eight men and eight women). PROTOCOL: Fasted subjects received subcutaneous injections of ghrelin (3.6 nmol/kg) or saline. After 30 min, a buffet breakfast was served. RESULTS: Ghrelin injection increased energy intake by 27% (ghrelin 5076 +/- 691 kJ versus saline 4230+/-607 kJ, P = 0.04). Ghrelin appeared to enhance the perceived palatability of the food offered (palatability score: ghrelin 81.1 +/- 3.6 versus saline 70.0 +/- 4.4; P = 0.03). CONCLUSIONS: These results suggest that subcutaneous ghrelin is effective at stimulating energy intake and improving palatability and may be of direct use in the treatment of appetite loss.     

Leptin and ghrelin in relation to Helicobacter pylori status in adult males

CONTEXT: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. OBJECTIVE: We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin. DESIGN, SETTING, AND PATIENTS: We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center. OUTCOMES: We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs. RESULTS: Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P < 0.0001 and r = 0.35; P < 0.0001, respectively) and H. pylori- (r = 0.65; P < 0.0001 and r = 0.41; P < 0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (<80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P < 0.0001). CONCLUSIONS: These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.     

Effect of resistance exercise, with or without carbohydrate supplementation, on plasma ghrelin concentrations and postexercise hunger and food intake

The effects of resistance exercise with and without carbohydrate (CHO) supplementation on hunger, postexercise food intake, and plasma ghrelin, an orexigenic gastric peptide, are poorly characterized. We examined the individual and combined effects of a resistance exercise bout and CHO consumption on plasma ghrelin and postexercise food intake. Twenty-one apparently healthy young male participants ([mean ± SD] age = 20 ± 1.8 years, body mass index = 24.8 ± 3.3 kg/m²) completed in random order 3 treatment conditions: (1) ExCHO—80-minute resistance exercise bout while consuming CHO (∼77 g CHO, 306 kcal); (2) ExPLA—identical exercise with a noncaloric placebo; and (3) NoExCHO—no-exercise trial of quiet sitting and CHO consumption. Blood samples were obtained before, during, and immediately postexercise, and 110 minutes after exercise. At 2 hours postexercise, they were provided a buffet of food from which they ate ad libitum. There was a significant time × treatment interaction for plasma ghrelin caused by a decline from pre- to postexercise in the 2 exercise conditions compared with an increase over time in the NoExCHO condition. At 110 minutes postexercise, ghrelin was 21% and 13% lower in ExCHO and ExPLA compared with NoExCHO (both Ps < .05). However, despite the lower ghrelin concentrations for the 2 exercise conditions, the subjective ratings of hunger were not lower for these conditions compared with the NoExCHO. There were no differences in absolute ad libitum energy intake from the buffet among the 3 conditions, but relative energy intake from the buffet accounting for the estimated cost of exercise was lowest among the 2 exercise conditions. We conclude that (1) weight lifting lowers plasma ghrelin concentrations during exercise and attenuates its rise during the postexercise period in young men and (2) the lower plasma ghrelin concentration is not associated with lower subjective feelings of hunger measured 100 minutes postexercise, but is associated with a lower relative food intake.