Plasma Ghrelin Concentrations Research Articles

Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations

Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague–Dawley rats were fed with a high-fat (HF) diet for 8weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin (r=0.402, P=0.028), CCK (r=−0.518, P=0.003) and leptin concentration (r=−0.514, P=0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations.

Fall in plasma ghrelin concentrations after cisplatin-based chemotherapy in esophageal cancer patients

Chemotherapeutic agents, especially cisplatin, cause severe gastrointestinal disorders, including nausea, vomiting, and anorexia, which markedly impair quality of life and encourage discontinuation of chemotherapy. Since cisplatin was recently reported to decrease plasma ghrelin and food intake in rodents, we monitored the plasma ghrelin level and its association with nutritional status and adverse events during chemotherapy in patients with esophageal cancer. Twenty patients with advanced esophageal cancer who underwent cisplatin-based neoadjuvant chemotherapy were enrolled in a prospective observational study. Changes in gastrointestinal hormones including ghrelin were measured and correlated with feeding activity, including appetite and dietary intake, nutritional status including rapid turnover proteins, and adverse events from chemotherapy. Plasma total ghrelin significantly decreased at days 3 and 8 of chemotherapy but recovered at day 28 (baseline: 140 ± 54; day 3: 107 ± 46; day 8: 82 ± 32; day 28: 126 ± 43 fmol/ml; p = 0.023 for day 3 and p = 0.034 for day 8). No changes were noted in plasma leptin (baseline: 3.2 ± 1.8; day 8: 2.5 ± 1.5 ng/ml; p = 0.18). Among blood nutritional parameters, transferrin was the only parameter that decreased significantly and its decline, as well as loss of oral intake and appetite, correlated significantly with plasma ghrelin levels (p = 0.0013, p = 0.0063, and p = 0.013, respectively). Neutropenia and anorexia were more frequent in patients with low plasma ghrelin than in those with high plasma ghrelin (p = 0.015 and p = 0.011, respectively). Cisplatin-based chemotherapy significantly reduced plasma ghrelin and feeding activity. Ghrelin is a potentially useful novel therapy for minimizing the adverse effects of chemotherapy.

Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism.

To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylori). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ alone, mice were given a subcutaneous infusion of IFNγ for 7 d. Finally, the influence of IFNγ and somatostatin on the ghrelin promoter was characterized. H. pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models. Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ. Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression. IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.

Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain

Data from species other than cattle indicate that ghrelin and GH secretagogue receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or glucose metabolism by directly affecting liver and adipose tissue metabolism. Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose tissues differ in steers exhibiting differences in composition of gain. At trial initiation (d 0), 8 steers were slaughtered for initial carcass composition. The remaining 64 steers were stratified by BW, allotted to pen, and treatment was assigned randomly to pen. Steers were not implanted with anabolic steroids. Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111 d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d; LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth, tenth, and eleventh rib sections were dissected for chemical composition and regression equations were developed to predict compositional gain. Liver, muscle, and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent Western blotting for GHS-R. Replicate blood samples collected before each slaughter were assayed for ghrelin and leptin concentrations. When compared at a common compositional fat end-point, the rate of carcass fat accretion (g·kg of shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of carcass protein accretion (g·kg of shrunk BW(-1)) was less (P < 0.001) compared with LE-HE steers. When compared at a common compositional fat end-point, plasma leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds, increased over time in liver and adipose tissue but did not differ as a result of treatment. Plasma ghrelin concentrations were increased for cattle continuously fed the HE diet as they became increasingly fatter; however, abundance of the GHS-R in liver, muscle, and subcutaneous adipose tissue was not different between treatment groups. The role of ghrelin in cattle metabolism warrants further investigation as it could have a significant effect on composition of BW gain, feed efficiency, and metabolic disorders such as ketosis and fatty liver.

La reducción del sueño como factor de riesgo para obesidad

Nocturnal sleep patterns may be a contributing factor for the epidemic of obesity. Epidemiologic ana experimental studies have reported that sleep restriction is an independent risk factor for weight gain and obesity. Moreover, sleep restriction is significantly associated with incidence and prevalence of obesity and several non-transmissible chronic diseases. Experimental sleep restriction is related to altered plasma leptin and ghrelin concentrations. Both hormones are directly related to appetite and satiety mechanisms. Also, a higher activity of the orexin/hypocretin system has been reported, as well as changes in glucose metabolism and autonomic nervous system. Some studies indicate that these endocrine changes could be associated with a higher diurnal food intake and preference for energy- dense foods. All these changes could result in a positive energy balance, leading to weight gain and a higher obesity risk in the long-term. The present article summarizes the epidemiologic and experimental evidence related to sleep deprivation and higher obesity risk. The possible mechanisms are highlighted.

Sleep deprivation as a risk factor for obesity

Nocturnal sleep patterns may be a contributing factor for the epidemic of obesity. Epidemiologic ana experimental studies have reported that sleep restriction is an independent risk factor for weight gain and obesity. Moreover, sleep restriction is significantly associated with incidence and prevalence of obesity and several non-transmissible chronic diseases. Experimental sleep restriction is related to altered plasma leptin and ghrelin concentrations. Both hormones are directly related to appetite and satiety mechanisms. Also, a higher activity of the orexin/hypocretin system has been reported, as well as changes in glucose metabolism and autonomic nervous system. Some studies indicate that these endocrine changes could be associated with a higher diurnal food intake and preference for energy- dense foods. All these changes could result in a positive energy balance, leading to weight gain and a higher obesity risk in the long-term. The present article summarizes the epidemiologic and experimental evidence related to sleep deprivation and higher obesity risk. The possible mechanisms are highlighted.

Acute sleep deprivation reduces energy expenditure in healthy men

Epidemiologic evidence indicates that chronic sleep curtailment increases risk of developing obesity, but the mechanisms behind this relation are largely unknown. We examined the influence of a single night of total sleep deprivation on morning energy expenditures and food intakes in healthy humans. According to a balanced crossover design, we examined 14 normal-weight male subjects on 2 occasions during a regular 24-h sleep-wake cycle (including 8 h of nocturnal sleep) and a 24-h period of continuous wakefulness. On the morning after regular sleep and total sleep deprivation, resting and postprandial energy expenditures were assessed by indirect calorimetry, and the free-choice food intake from an opulent buffet was tested in the late afternoon at the end of the experiment. Circulating concentrations of ghrelin, leptin, norepinephrine, cortisol, thyreotropin, glucose, and insulin were repeatedly measured over the entire 24-h session. In comparison with normal sleep, resting and postprandial energy expenditures assessed on the subsequent morning were significantly reduced after sleep deprivation by ≈5% and 20%, respectively (P < 0.05 and P < 0.0001). Nocturnal wakefulness increased morning plasma ghrelin concentrations (P < 0.02) and nocturnal and daytime circulating concentrations of thyreotropin, cortisol, and norepinephrine (P < 0.05) as well as morning postprandial plasma glucose concentrations (P < 0.05). Changes in food intakes were variable, and no differences between wake and sleep conditions were detected. Our findings show that one night of sleep deprivation acutely reduces energy expenditure in healthy men, which suggests that sleep contributes to the acute regulation of daytime energy expenditure in humans.

Ghrelin and its promoter variant associated with cardiac hypertrophy

The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

Plasma ghrelin concentration is decreased by short chain fatty acids in wethers

To examine the effects of short chain fatty acids (SCFAs) on plasma ghrelin concentration, 4 wethers were injected intravenously with SCFA solutions [acetate (ACE), propionate (PRO), and butyrate (BUT) (0.8 mmol/kg BW)] and saline. The experiment was conducted after a 4 × 4 Latin square design. Each solution was injected into the jugular vein catheter with blood samples taken at −10, 0, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min relative to the injection time also from this catheter. Plasma ghrelin concentrations decreased after injection with ACE, PRO, and BUT. Although plasma glucose concentrations increased after injection with PRO and BUT ( P < 0.05), the increment areas were greater with BUT than with PRO. Plasma insulin concentrations increased after injection with PRO and BUT ( P < 0.05). The decrement areas in plasma ghrelin concentrations were equal in ACE, PRO, and BUT. These data suggest that SCFAs inhibit ghrelin secretion in wethers and not through increased circulating glucose and insulin as previously proposed.

반복적인 모형마 운동에 따른 기수의 혈장 그렐린과 호르몬들의 관계

이 연구 목적은 기수를 대상으로 공복 시 반복적인 모의 경주마 운동 시 그렐린과 관련 호르몬의 관계를 규 명하고자 한다. 공복의 기수와 기수후보생들은 경마의 첫 번째 단거리 1000 m, 두 번째 중거리 1700 m 세 번째 장 거리 2300 m의 반복적인 모의 경주마 운동 전과 직후 정맥혈을 채혈하여 그렐린, 렙틴, 인슐린, IGF-I과 코티졸을 분 석하였다. 피어슨 상관관계에서 기수후보생이 3차 운동 후 글레린과 인슐린 농도가 r= .55를 나타내었다. 기수의 운동 전 글레린과 렙틴 농도가 r= .73으로 운동전 글레린 렙틴 수준이 통계적으로 유의성(p<.05) 있는 관계와 기수후보생 이 글레린과 코티졸 농도에서 r= .64를 나타내었다. 글레린 렙틴 인슐린 IGF-1 농도는 운동전에 비교하여 통계적으로 유의성 없이 1차 운동 후 증가와 2차, 3차 감소, 경마기수와 후보생보도 통계적으로 유의성 없는 차이를 나타내었다. 경마기수에 비교 하여 후보생은 1차 2차, 3차 운동에서 통계적으로 유의성 있게 IGF-1는 낮게(p<.05) 코티졸 농도는 높게(p<.001) 나타내었다. 연구결과 반복적인 모의 경주마 운동으로 인한 에너지 소모 반응에서 기수후보생의 3차 운 동에서 만이 글레린과 인슐린의 상관관계를 나타내었다.

Alterations in Downstream Mediators Involved in Central Control of Eating Behavior in Obese Adolescents Submitted to a Multidisciplinary Therapy

The aim of this study was to verify the effects of a multidisciplinary therapy (24 weeks) on neurohormonal control of food intake, specifically in orexigenic (total ghrelin, agouti-related protein [AgRP], neuropeptide Y [NPY], and melanin-concentrating hormone) and anorexigenic factors (leptin, insulin, and alpha-melanocyte stimulating hormone [α-MSH]), in obese adolescents. A total of 88 adolescents (38 boys and 50 girls), including 62 obese and 26 normal-weight, aged 15-19 years were recruited. Obese adolescents were submitted to a 24-week multidisciplinary therapy. AgRP, NPY, melanin-concentrating hormone, leptin, insulin, glucose, α-MSH, total ghrelin, and food intake were measured at three stages (at baseline, after 12 weeks, and after 24 weeks). At baseline, obese adolescents showed hyperleptinemia (circulating leptin levels, which were, in boys and girls, 40 and 35 times higher than in normal-weight subjects, respectively). After 24 weeks, these values decreased in all obese patients. Our results showed no differences in ghrelin levels between obese and normal-weight adolescents, in both genders. However, obese boys reduced their plasma ghrelin concentration after 24 weeks of therapy (p < .05). The multidisciplinary therapy decreased NPY and AgRP values and increased α-MSH; simultaneously with these changes there was a decrease in total food intake after 24 weeks of therapy. We can conclude that the multidisciplinary therapy was efficient to modulate neurohormonal control of food intake in obese adolescents.

Ghrelin, Resistin and Leptin Levels in Patients with Metabolic Syndrome

Aim: This study was designed to compare the fasting ghrelin, leptin and resistin levels between metabolic syndrome (MS) patients with healthy controls. Method: This trial was performed on 21 patients with MS (7 men; mean age, 44±4 years) and 17 healthy controls (8 men; mean age, 43±3 years). Diagnosis of MS was defined based on National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. Patients meeting at least 3 of the MS criteria, with a body mass index (BMI) ≥30 kg/m² were included in the MS group. Among healthy volunteers, those with a BMI<30 kg/m² were selected as the control group. Plasma ghrelin, serum leptin and resistin concentrations were measured by ELISA method. Result: Ghrelin levels were similar between MS and control groups. There was a negative correlation detected between ghrelin levels with BMI and leptin levels (r=-.54, P=.01 and r=-.56, P=.009, respectively). Resistin levels were found similar between MS with control groups. Leptin levels were significantly higher at the MS group than control group (35±17 ng/ml vs. 14±8 ng/ml, P=.001). Leptin levels had a positive correlation with BMI (r=.56; P=.008). Conclusion: We have demonstrated that leptin levels in MS group were higher than control group. However, ghrelin and resistin levels were similar to control group. In addition, we have showed leptin levels has a positive correlation with BMI and a negative correlation with ghrelin levels.

Feeding behavior and performance of lambs are influenced by flavor diversity1,2

This study determined whether early experiences of sheep with the same feed, but presented in multiple or single flavors, would influence intake, the profile of hormones involved in feed intake regulation, and the subsequent acceptability of novel feeds. Thirty-five 2-mo-old lambs were randomly assigned to 5 treatments (7 lambs/treatment). Lambs in 1 treatment (the diversity treatment) were simultaneously fed an unflavored plain ration of alfalfa (control) and barley (75:25; as-fed basis) and the same ration mixed (0.2%) with 1 of 3 flavors: 1) sweet, 2) umami, or 3) bitter. The other 4 treatments (monotonous diets) received only 1 of the 4 rations. All animals were fed their respective rations from 0800 to 1600 h for 60 d. On d 55, intake was recorded every 30 min for 8 h. On d 58, blood samples from lambs were collected at 1 h prefeeding and at 30, 60, 210, 300, and 540 min postfeeding. Preference tests were conducted by simultaneously offering novel feeds: 1) high-energy feed, 2) high-protein feed, 3) beet pulp mixed with phytochemicals, or 4) low-quality feed. Lambs in the diversity treatment consumed more feed than did lambs in the other treatments (P < 0.001). Lambs in the diversity treatment consumed equivalent amounts of plain and umami feeds, with a greater amount (P < 0.001) of the umami feed being consumed than the bitter and sweet feeds. Lambs in the diversity treatment tended to grow faster than did lambs in the other treatments (P=0.06). On d 55, lambs in the diversity treatment showed decreased (P < 0.05) feed intake compared with lambs in the other treatments during the 2 peaks of food consumption (30 and 270 min from feeding) and showed a trend for the least plasma concentrations of ghrelin (P=0.06). In contrast, lambs in the diversity treatment consumed more feed than did lambs exposed to monotonous flavors at 60, 90, 120, and 180 min from feeding (P < 0.05). Lambs in the diversity treatment also showed the least concentrations of cholecystokinin and glucagon-like peptide 1 (P < 0.001). There were trends for the greatest concentrations of leptin (P=0.14) and IGF-1 (P=0.16) in the diversity treatment, and for the least concentration of leptin in the bitter treatment (P=0.14). Previous experience with flavored feeds affected the preference of lambs for high-energy and low-quality feeds, and for beet pulp mixed with phytochemicals (treatment × feed × day effect; P < 0.05). Thus, exposure to diverse flavors has the potential to increase feed intake and induce a more even consumption of feed across time by reducing peaks and nadirs of intake compared with exposure to monotonous rations. Flavor diversity may also influence the initial acceptability of and preference for novel feeds.

Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

Background Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss.Methodology/Principal FindingsWe recruited 1495 overweight/obese subjects (BMI: 25–40 kg/m2) of 20–65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12–14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes.Conclusions/SignificanceSleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors.

Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4weeks later when the tumor represented 1–2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.

Significant lowering of plasma ghrelin but not des-acyl ghrelin in response to acute exercise in men

Ghrelin, an acylated peptide produced predominantly in the stomach, stimulates feeding and growth hormone (GH) secretion via interaction with the GH secretagogue receptor. Ghrelin molecules are present in two major endogenous forms, an acylated form (ghrelin) and a des-acylated form (des-acyl ghrelin). Recent studies indicated that aerobic exercise did not change plasma total ghrelin levels, however, dynamics of circulating ghrelin and des-acyl ghrelin during aerobic exercise remains unclear. The purpose of this study is to examine the effects of moderate intensity exercise on plasma ghrelin and des-acyl ghrelin concentrations, and to investigate the relationship between ghrelin molecules and other hormonal and metabolic parameters during exercise. Nine healthy males (25.2 ± 0.5 years) exercised for 60 min at 50% of their maximal oxygen consumptions. We measured the plasma concentrations of ghrelin, des-acyl ghrelin, GH, norepinephrine (NE), epinephrine (E), dopamine (DA), insulin, and glucose. Plasma ghrelin level significantly decreased during exercise, whereas plasma des-acyl ghrelin and total ghrelin levels did not change. Plasma NE, E, DA and GH levels were significantly increased during exercise. Plasma insulin level significantly decreased during exercise, and plasma glucose levels remained steady during exercise. NE, E, DA, and GH were correlated negatively with plasma ghrelin levels. These findings suggest that acute moderate exercise may suppress ghrelin release from the stomach, decrease ghrelin O-acyltransferase activity, and/or activate ghrelin utilization in peripheral tissues and that exercise-induced ghrelin suppression may be mediated by activated adrenergic system.

Effect of ginger on gastric motility and symptoms of functional dyspepsia.

To evaluate the effects of ginger on gastric motility and emptying, abdominal symptoms, and hormones that influence motility in dyspepsia. Eleven patients with functional dyspepsia were studied twice in a randomized double-blind manner. After an 8-h fast, the patients ingested three capsules that contained ginger (total 1.2 g) or placebo, followed after 1 h by 500 mL low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires, and blood was taken for measurement of plasma glucagon-like peptide-1 (GLP-1), motilin and ghrelin concentrations, at intervals throughout the study. Gastric emptying was more rapid after ginger than placebo [median (range) half-emptying time 12.3 (8.5-17.0) min after ginger, 16.1 (8.3-22.6) min after placebo, P≤0.05]. There was a trend for more antral contractions (P=0.06), but fundus dimensions and gastrointestinal symptoms did not differ, nor did serum concentrations of GLP-1, motilin and ghrelin. Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia, but had no impact on gastrointestinal symptoms or gut peptides.

Energy homeostasis regulatory peptides in hibernating grizzly bears

Grizzly bears ( Ursus arctos horribilis) are inactive for up to 6 months during hibernation. They undergo profound seasonal changes in food intake, body mass, and energy expenditure. The circa-annual regulation of metabolism is poorly understood. In this study, we measured plasma ghrelin, leptin, obestatin, and neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of energy homeostasis, in ten grizzly bears. Blood samples were collected during the active summer period, early hibernation and late hibernation. Plasma levels of leptin, obestatin, and NPY did not change between the active and the hibernation periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly decreased during the inactive winter period compared to summer levels. The elevated ghrelin levels may help enhance body mass during pre-hibernation, while the low plasma ghrelin concentrations during hibernation season may contribute to the maintenance of hypophagia, low energy utilization and behavioral inactivity. Our results suggest that ghrelin plays a potential role in the regulation of metabolic changes and energy homeostasis during hibernation in grizzly bears.

Short-, moderate-, and long-term treadmill training protocols reduce plasma, fundus, but not small intestine ghrelin concentrations in male rats

It has been suggested that circulating ghrelin levels are upregulated by fasting, hypoglycemic status, and a physical exercise-induced energy deficit. The purpose of the present study was to investigate the timecourse adaptations of the plasma, fundus, and small intestine ghrelin concentrations as well as related hormones and liver ATP levels to 3, 6, and 12 weeks of treadmill endurance running. Thirty-nine male Wistar rats (12-14 weeks old) were randomly assigned to 3 control (C3, no.=5; C6, no.=7 and C12, no.=7) and 3 training groups (E3, no.=6; E6, no.=7 and E12, no.=7). The rats in the 3 training groups were exercised on a motor-driven treadmill at 25 m/min (0% grade) for 60 min/day, 5 days/week for 3, 6, and 12 weeks, respectively. The animals were sacrificed 48 h after the last session of each training program and tissues were analyzed. Total ghrelin concentrations were significantly (p<0.05) lower in trained rat plasma and fundus tissue after all treadmill endurance running programs. Small intestine ghrelin concentrations remained unchanged. Plasma GH concentrations and liver ATP content were significantly higher in E6 and E12 groups. Data indicate that as little as 3 weeks of moderate treadmill exercise reduces plasma and fundus total ghrelin concentrations with elevated plasma GH and liver ATP content occurring after 6 and 12 weeks of training. Exercise training-induced improvement of energy source availability and negative feedback from increased GH levels may play a role in reducing plasma and fundus ghrelin levels.

Milk supplementation facilitates appetite control in obese women during weight loss: a randomised, single-blind, placebo-controlled trial

Dairy products provide Ca and protein which may facilitate appetite control. Conversely, weight loss is known to increase the motivation to eat. This randomised controlled trial verified the influence of milk supplementation on appetite markers during weight loss. Low Ca consumer women participated in a 6-month energy-restricted programme (-2508 kJ/d or -600 kcal/d) and received either a milk supplementation (1000 mg Ca/d) or an isoenergetic placebo (n 13 and 12, respectively). Fasting appetite sensations were assessed by visual analogue scales. Anthropometric parameters and fasting plasma concentrations of glucose, insulin, leptin, ghrelin and cortisol were measured as well. Both groups showed a significant weight loss (P < 0·0001). In the milk-supplemented group, a time x treatment interaction effect showed that weight loss with milk supplementation induced a smaller increase in desire to eat and hunger (P < 0·05). Unlike the placebo group, the milk-supplemented group showed a lower than predicted decrease in fullness (-17·1 v. -8·8; -2·7 v. 3·3 mm, P < 0·05, measured v. predicted values, respectively). Even after adjustment for fat mass loss, changes in ghrelin concentration predicted those in desire to eat (r 0·56, P < 0·01), hunger (r 0·45, P < 0·05) and fullness (r -0·40, P < 0·05). However, the study did not show a between-group difference in the change in ghrelin concentration in response to the intervention. These results show that milk supplementation attenuates the orexigenic effect of body weight loss.