Key Spec Table
|Analytes Available||Species Reactivity||Key Applications||Detection Methods|
|Description||Human Ghrelin (TOTAL) RIA|
|Background Information||Ghrelin is a recently discovered hormone is secreted primarily by the stomach in response to glucose administration or CNS signals.|
|Detection method||125I Radioactive|
|Linearity of Dilution||99–146%|
|Safety Information according to GHS|
|Storage and Shipping Information|
|GHRELIN (Total) RIA KIT - 125 TUBES (Cat. # GHRT-89HK)|
References | 26 Available | See All References
|Reference overview||Pub Med ID|
|Reverse Feeding Suppresses the Activity of the GH Axis in Rats and Induces a Preobesogenic State. |
Glad CA, Kitchen EE, Russ GC, Harris SM, Davies JS, Gevers EF, Gabrielsson BG, Wells T
Endocrinology 152 869-82. Epub 2011 Jan 5. 2011
Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P < 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4-5%; P < 0.01) and terminal liver weight (by 11%; P < 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P < 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P < 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P < 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P < 0.05) and retroperitoneal WAT weight (by 72%; P < 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P < 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.
|Cereal type and heat processing of the cereal affect nutrient digestibility and dynamics of serum insulin and ghrelin in weanling pigs. |
Menoyo D, Serrano MP, Barrios V, Valencia DG, Lázaro R, Argente J, Mateos GG
Journal of animal science 2011
The effects of feeding corn or rice, either raw or heat processed (HP), on apparent total tract digestibility (ATTD) and apparent ileal digestibility (AID) of nutrients and insulin and ghrelin concentrations in the serum were studied in young pigs. Pigs were weaned at approximately 23 ± 3 d of age and weighed 7.4 ± 1.2 kg. Each of the 4 treatments was replicated 9 times and the experimental unit was a pig individually housed. Pigs (5 males and 4 females/treatment) were fed their respective diets ad libitum from 23 to 47 d of age. At 37 d of age, the effects of dietary treatments on the fasting and postprandial concentrations of insulin and total and acylated ghrelin were studied. The ATTD of OM, GE, and ether extract (EE) was, respectively, 4.3, 5.4, and 3.6% greater (P < 0.05) for the rice than for the corn diets but CP digestibility was not affected. Similar results were observed for AID. Heat processing of the cereal increased (P < 0.05) the ATTD by 2.1% for OM, 3.2% for GE, 7.1% for EE, and 2.2% for CP and tended to increase the AID of CP (P = 0.06) and starch (P = 0.09). The postprandial serum insulin response was greater and prolonged in pigs fed raw rice than pigs fed raw corn (P < 0.05). Also, the effects of HP on serum insulin response were more pronounced with corn than with rice (cereal x HP, P < 0.05). Total ghrelin concentration was not affected by treatment but acylated ghrelin was greater (P < 0.05) at 6 h postprandial in pigs fed rice than pigs fed raw corn. Feeding rice and HP corn increased nutrient digestibility and insulin response in the early postprandial period and acylated ghrelin response in the late postprandial period compared with feeding raw corn.
|Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects. |
Holmer-Jensen J, Hartvigsen ML, Mortensen LS, Astrup A, de Vrese M, Holst JJ, Thomsen C, Hermansen K
European journal of clinical nutrition 2011
Background/Objectives:Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design.Subjects/Methods:A total of 11 obese non-diabetic subjects (age: 44-74, BMI: 30-41.4 kg m(-2)) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured.Results:We observed no statistically significant (P=0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P=0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins.Conclusion:We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.European Journal of Clinical Nutrition advance online publication, 27 July 2011; doi:10.1038/ejcn.2011.142.
|Metabolic maturity at birth and neonate lamb survival: Association among maternal factors, litter size, lamb birth weight, and plasma metabolic and endocrine factors on survival and behavior. |
DR Miller, D Blache, RB Jackson, EF Downie, JR Roche
Journal of animal science 88 581-93 2010
This paper reports an investigation into metabolic and endocrine maturity in the neonate lamb and the relationships between litter size, birth weight, and maternal metabolic and endocrine variables on behavior at birth and survival over the first 72 h of life. Data were from multiparous, fine-wool Merino ewes (n = 150; equal numbers of single-lamb and twin-lamb bearing status) lambed on pasture after late gestational glucocorticoid treatments. Stepwise multiple regression analysis was used to investigate relationships between lamb survival, behavior, endocrinology, and physiology. Improved lamb viability at 72 h after birth was related to decreased chill indices at birth, singleton litter status, greater presuckling rectal temperature, increased ewe prelambing plasma ghrelin concentration, female sex, heavier birth weight, and decreased lamb presuckling plasma glucose concentration. Greater rectal temperatures were associated with heavier birth weight and gestation lengths shorter than 146 d, but no relationship with neonatal behavioral progression was evident. Presuckling glucose concentrations were greater in singletons and lambs born to ewes of greater BCS at d 95 of gestation, and lambs of heavier birth weight, but were also associated with decreased rectal temperatures. This might reflect a delay in glucose utilization during the adjustment from a fetal metabolic rate to a rate appropriate for cold external environments. Singleton lambs exhibited decreased presuckling plasma NEFA concentrations and were almost 8 times more likely to survive to 72 h than a twin-born lamb. Birth weight was lesser in lambs born to ewes with elevated plasma glucose and leptin concentrations before lambing and was positively related to ewe BW at d 95 of gestation and to length of gestation. Greater presuckling plasma ghrelin and leptin concentrations were measured for shorter gestation lengths. Neonate presuckling ghrelin concentrations above 650 pg/mL tended (P = 0.077) to be associated with improved lamb survival to 72 h. This was consistent with a curvilinear decline in neonate survival rates to 72 h after birth as time of latency to suckle increased. No relationship was observed between lamb plasma glucose concentrations and behavioral expression after lambing. Lambs exhibiting greater metabolic and endocrine maturity at birth had improved survival in a cold environment to 72 h after birth. The role of ghrelin in ovine fetal development warrants further investigation.
|Effects of fat supplementation on postprandial GIP, GLP-1, ghrelin and IGFBP-1 levels: a pilot study on adolescents with type 1 diabetes. |
M Lodefalk,C Carlsson-Skwirut,J J Holst,J Aman,P Bang
Hormone research in pædiatrics 73 2010
Aims: To compare the responses of GIP, GLP-1, ghrelin and IGFBP-1 between meals with different fat and energy content in adolescents with type 1 diabetes (T1DM) and to relate them to gastric emptying and glycaemia. Methods: On different days and in a random order, 7 adolescents with T1DM ingested a high- and low-fat meal (fat content: 38 and 2 g, energy content: 640 and 320 kcal, respectively). At normoglycaemia, the same prandial insulin dose was given at both meals and to all subjects. Postprandial blood samples were taken repeatedly over 4 hours. Gastric emptying was estimated by the paracetamol absorption method. Results: The area under the curve (AUC) for GIP(0-240 min) and for GLP-1(0-120 min) was larger, but smaller for relative ghrelin(0-240 min), after the high-fat meal (p = 0.002, 0.030 and 0.043, respectively). IGFBP-1 decreased significantly, but not differently, after the meals. Larger GLP-1 secretion correlated with slower gastric emptying (p = 0.029) and higher fasting ghrelin levels correlated with lower postprandial glycaemia (p = 0.007). Conclusion: In adolescents with T1DM, the postprandial responses of GIP, GLP-1 and ghrelin, but not that of IGFBP-1, depend more on meal size than on insulin.
|Basal Plasma Levels of Insulin, Leptin, Ghrelin, and Amylin Do Not Signal Adiposity in Rats Recovering from Forced Overweight. |
Gloy VL, Lutz TA, Langhans W, Geary N, Hillebrand JJ
This study examined how adiposity signals are related to adiposity during recovery from forced overweight (OW). Rats were rendered OW by chronic intragastric overfeeding (OW). Overfeeding was stopped when OW rats reached 126-129% of saline-infused normal-weight (NW) rats. Adipose tissue (AT) mass was estimated by computed tomography, and blood was drawn from chronic atrial cannulas throughout. Basal levels (i.e. after 2-3 h fasts late in the diurnal phase) of the hypothesized adiposity signals insulin, leptin, ghrelin, and amylin were assayed. OW rats gained approximately 130 g more body weight (BW) and approximately 100 g more AT mass during overfeeding. Plasma levels of insulin and leptin increased, whereas those of ghrelin decreased, linearly with AT mass; amylin did not change reliably. During recovery, OW rats' BW and AT mass decreased but were still elevated vs. NW rats after 39 d. OW rats' insulin returned to NW levels on d 1 of recovery and decreased below NW levels thereafter. Leptin was no longer elevated after d 8 of recovery. Ghrelin and amylin did not change reliably during recovery. Although AT mass decreased in OW rats during each intermeasurement interval between d 0 and d 23 of recovery, insulin and leptin did so during only the first interval (d 0-5). Insulin and leptin levels were exponentially related to AT mass during recovery. These data indicate that basal insulin, leptin, ghrelin, and amylin do not encode AT mass in rats dynamically regulating BW and adiposity during recovery from OW.
|Comparison of Competitive Radioimmunoassays and Two-Site Sandwich Assays for the Measurement and Interpretation of Plasma Ghrelin Levels. |
Prudom C, Liu J, Patrie J, Gaylinn BD, Foster-Schubert KE, Cummings DE, Thorner MO, Geysen HM
The Journal of clinical endocrinology and metabolism 2010
Context: Ghrelin, an endogenous ligand for the GH secretagogue receptor, is an orexigenic peptide hormone produced primarily by the stomach. Recent studies suggest significant differences in the specificity of currently available ghrelin assays. Objective: The aim of the study was to compare four ghrelin assays (two commercially available and two developed by our group) of differing specificity, each used on the same set of more than 800 plasma samples from a human study. Design: Thirteen volunteers were sampled every 20 min for 6 h after consumption of one of three isocaloric drinks consisting of either 80% fat, 80% carbohydrate, or 80% protein. The samples were assayed by RIA for total and active ghrelin, as well as by sandwich assays for acyl and des-acyl ghrelin. The ghrelin profiles for each individual were smoothed using a statistical algorithm to lessen the effects of pulsatility and noise. Results: The sandwich assays for acyl and des-acyl ghrelin yielded ghrelin values that were lower than those from the corresponding RIAs. The ghrelin profiles after nutrient ingestion were similar, yet key differences among the four assays were apparent; in particular, percentage changes were significantly greater in the sandwich assays. Conclusions: The lower levels and greater relative changes in ghrelin values reported by the sandwich assays are consistent with greater assay specificity. When applied to the nutrient study, the sandwich assays were better able to distinguish the different responses to different nutrients than were the RIAs.
|Ghrelin, paraoxonase and arylesterase levels in depressive patients before and after citalopram treatment. |
Abdullah Onder Barim, Suleyman Aydin, Ramis Colak, Ersel Dag, Omer Deniz, Ibrahim Sahin
Clinical biochemistry 42 1076-81 2009
OBJECTIVES: The purpose of this study was to examine alterations in lipid profiles and in the serum concentrations of acylated and desacylated ghrelin, paraoxonase and arylesterase in psychiatric patients before and after treatment with 40 mg citalopram daily for 3 months. DESIGN AND METHODS: Samples were collected from 22 healthy controls and 24 psychiatric patients before and after citalopram treatment. Blood levels of acylated and desacylated ghrelin were measured by radioimmunoassay. Paraoxonase and arylesterase activities were determined spectrophotometrically. Lipid parameters were measured on the OLYMPUS-AU400. RESULTS: It was found that the levels of acylated, desacylated ghrelin, paraoxonase arylesterase, total cholesterol and triglyceride were lower in depressive patients before citalopram treatment than in the control group. Those parameters were not restored after citalopram treatment except for the arylesterase level. CONCLUSION: Decreased PON1 and ghrelin levels as well as fluctuations in lipid profiles may be involved in the etiology of depressive disorders.
|Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. |
Borer, Katarina T, et al.
J. Clin. Endocrinol. Metab., 94: 2290-8 (2009) 2009
CONTEXT: It is uncertain how between-meal variations in energy availability and physiological changes in ghrelin, leptin, and insulin affect appetite. Objective: The aim of the study was to examine the influence on human appetite of the meal size and its nutrient content or changes in energy availability and concentrations of ghrelin, leptin, and insulin. DESIGN: We conducted a crossover study manipulating meal size and energy availability through exercise energy expenditure and iv nutrient replacement (TPN). Setting: The study was performed at a Clinical Research Center. PARTICIPANTS: Ten healthy postmenopausal women (age, 59.7 +/- 1.5 yr; mean body mass index, 26 kg/m(2)) were studied. Interventions: We conducted trials based on different morning meal size (418 vs. 2090 KJ), presence or absence of exercise energy expenditure (2273 to 2361 KJ), energy replacement by TPN (1521 to 1538 KJ), and a midday ad libitum meal. Main Outcome Measures: Changes in hunger, fullness, midday ad libitum food consumption, and concentrations of ghrelin, leptin, insulin, and metabolic fuels were measured. We also performed midday meal tests for the presence of caloric compensation. RESULTS: Appetite was influenced by the size and energy content of the meals, but not by variation in energy availability which also did not trigger consummatory compensation. Exercise reduced hunger and increased fullness. Ghrelin, leptin, and insulin responded to changes in energy availability but not to meal size. Appetite was unaffected by physiological changes in ghrelin, leptin, or insulin. CONCLUSIONS: During rest, appetite is influenced by the size and energy content of meals, but it bears no homeostatic relationship to between-meal changes in energy availability due to small meals, exercise, or TPN, or concentrations of ghrelin, leptin, and insulin.
|Metabolic maturity at birth and neonate lamb survival and growth: the effects of maternal low-dose dexamethasone treatment. |
D R Miller, R B Jackson, D Blache, J R Roche
Journal of animal science 87 3167-78 2009
Perinatal mortality is a major contributing factor to reproductive wastage in grazing sheep industries. Enhanced metabolic and endocrine maturity at birth may improve the behavioral competency and thermoregulatory ability of neonates, potentially improving lamb survival over the first 72 h of life. Maternal glucocorticoid treatment in late gestation was investigated as a mechanism for manipulating metabolic and endocrine maturity in the ovine neonate. Multiparous, fine-wool Merino ewes (n = 150) were divided into 3 groups to lamb on pasture. Within each group, 5 single-lamb and 5 twin-lamb bearing ewes were randomly allocated to 1 of 5 treatments. Treatments included a saline control (1 mL), or dexamethasone (2 mg/mL as the sodium phosphate) injected intramuscularly at 1 of 2 dose rates (1.5 or 3.0 mg) at d 130 or 141 of gestation. One-half of the control ewes were injected at d 130 and the remainder at d 141. Dexamethasone treatment had no effect on lamb survival to 72 h after birth, although there tended (P = 0.09) to be a smaller proportion of lambs dying due to dystocia than for control lambs. Heart girth at birth in singleton and twin lambs was reduced (P 0.01) at the greater dose rate. Further, treatment also reduced birth weight (by about 5%) and presuckling rectal temperatures in twin lambs, but not in singleton lambs. These reductions were also dependent on the sex of the lamb. Dexamethasone treatment did not alter gestation length or lamb presuckling plasma glucose, NEFA, urea, or leptin concentrations, but treatment at d 141 increased (P 0.05) ghrelin concentrations in singleton and male lambs. Behavioral interactions between ewes and neonatal lambs were generally unaffected, although treatment at d 130 produced lambs that took longer to bleat than lambs of untreated ewes (P 0.05). Treatment did not affect the concentration of measured blood metabolites or hormones at weaning. Although there were interactions between litter size, lamb sex, and the dose rate and time of treatment on weaning weight, BW recorded 73 d after weaning was unaffected by treatment. Despite changes in birth weight, rectal temperature, lamb behavior, and presuckling plasma ghrelin concentrations, survival in the first 72 h of life, and lamb growth performance were unaffected by periparturient maternal glucocorticoid treatment.
|High multivitamin intake by Wistar rats during pregnancy results in increased food intake and components of the metabolic syndrome in male offspring. |
Ignatius M Y Szeto, Alfred Aziz, Paul J Das, Ameer Y Taha, Nobuhiko Okubo, Sandra Reza-Lopez, Adria Giacca, G Harvey Anderson
American journal of physiology. Regulatory, integrative and comparative physiology 295 R575-82 2008
The effect of high multivitamin intake during pregnancy on the metabolic phenotype of rat offspring was investigated. Pregnant Wistar rats (n=10 per group) were fed the AIN-93G diet with the recommended vitamin (RV) content or a 10-fold increase [high vitamin (HV) content]. In experiment 1, male and female offspring were followed for 12 wk after weaning; in experiment 2, only males were followed for 28 wk. Body weight (BW) was measured weekly. Every 4 wk, after an overnight fast, food intake over 1 h was measured 30 min after a gavage of glucose or water. An oral glucose tolerance test was performed every 3-5 wk. Postweaning fasting glucose, insulin, ghrelin, glucagon-like peptide-1, and systolic blood pressure were measured. No difference in BW at birth or litter size was observed. Food intake was greater in males born to HV dams (P0.05), and at 28 wk after weaning, BW was 8% higher (P0.05) and fat pad mass was 27% higher (P0.05). Food intake reduction after the glucose preload was nearly twofold less in males born to HV dams at 12 wk after weaning (P0.05). Fasting glucose, insulin, and ghrelin were 11%, 62%, and 41% higher in males from HV dams at 14 wk after weaning (P0.05). Blood glucose response was 46% higher at 23 wk after weaning (P0.01), and systolic blood pressure was 16% higher at 28 wk after weaning (P0.05). In conclusion, high multivitamin intake during pregnancy programmed the male offspring for the development of the components of metabolic syndrome in adulthood, possibly by its effects on central mechanisms of food intake control.
|Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest. |
Gianni Biolo,Francesco Agostini,Bostjan Simunic,Mariella Sturma,Lucio Torelli,Jean Charles Preiser,Ginette Deby-Dupont,Paolo Magni,Felice Strollo,Pietro di Prampero,Gianfranco Guarnieri,Igor B Mekjavic,Rado Pisot,Marco V Narici
The American journal of clinical nutrition 88 2008
Physical inactivity is often associated with positive energy balance and fat gain.
|Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome. |
Kathleen De Waele, Stacey L Ishkanian, Roberto Bogarin, Charmaine A Miranda, Mohammad A Ghatei, Stephen R Bloom, Danièle Pacaud, Jean-Pierre Chanoine
European journal of endocrinology / European Federation of Endocrine Societies 159 381-8 2008
OBJECTIVE: Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS. DESIGN: A 56-week prospective, randomized, cross-over trial. METHODS: Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period. RESULTS: Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones. CONCLUSIONS: Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.
|Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene. |
Irene V Lambrinoudaki, George E Christodoulakos, Emmanuel V Economou, Sofia A Vlachou, Constantinos P Panoulis, Andreas P Alexandrou, Evangelia E Kouskouni, George C Creatsas
Maturitas 59 62-71 2008
BACKGROUND: Leptin and ghrelin are increasingly being recognized as cardiotropic hormones, promoting or inhibiting the atherosclerotic process, respectively. Apoptosis may be one pathway through which the actions of these hormones are mediated. Sex hormones are reported to influence the secretion and action of ghrelin and leptin. OBJECTIVE: To evaluate (1) the association of circulating ghrelin and leptin with selected markers of receptor-mediated apoptosis and (2) the effect of estrogen monotherapy, low dose estrogen-progestin therapy, tibolone and raloxifene on serum ghrelin and leptin in healthy postmenopausal women. METHODS: Eighty eight postmenopausal women aged 44-62 years were randomly allocated to daily (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5 mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum markers of apoptosis sFas, Fas-ligand (Fas-L) and caspase-1 were measured at baseline. Serum leptin and ghrelin were measured at baseline and at 3 months. RESULTS: Body Mass Index (BMI) and estradiol levels correlated positively, while FSH correlated negatively with serum leptin (BMI: r=0.646, p=0.005, estradiol: r=0.432, p=0.001, FSH: r=-0.401, p=0.002). Insulin levels associated positively with circulating leptin (r=0.394, p=0.011) and negatively with circulating ghrelin (r=-0.401, p=0.009). Serum leptin decreased significantly in E2/NETA group (baseline: 2.882+/-0.76 ng/ml, 3 months: 2.687+/-0.66 ng/ml, p=0.043), while it increased significantly in the raloxifene group (baseline: 2.671+/-0.54 ng/ml, 3 months: 2.839+/-0.47 ng/ml). Ghrelin levels decreased significantly only in the raloxifene group (baseline: 1634+/-592 pg/ml, 3 months: 1408+/-534 pg/ml). CONCLUSION: Apoptosis may be a pathway through which leptin exerts a pro-atherogenic effect. Low dose HT may act cardioprotectively by decreasing leptin levels in healthy recently menopaused women.
|Meal-induced compositional changes in blood and saliva in persons with bulimia nervosa. |
Anja W Dynesen, Allan Bardow, Arne Astrup, Birgit Petersson, Jens J Holst, Birgitte Nauntofte
The American journal of clinical nutrition 87 12-22 2008
BACKGROUND: Binge eating episodes in persons with bulimia nervosa may to some extent be a result of disturbed sensations of hunger and satiety. It has been hypothesized that abnormal appetite sensations may be due to bulimia nervosa-related alterations in the release of hormones that are known to be involved in the physiologic regulation of appetite and metabolism. OBJECTIVE: The objective was to investigate whether circulating concentrations of the appetite-regulating peptides leptin and ghrelin and markers of metabolism (glucose and insulin) are different in persons with bulimia nervosa than in controls before and after intake of a meal and whether these changes may be reflected in saliva. DESIGN: Twenty women with bulimia nervosa and 20 age- and sex-matched healthy controls participated. After an overnight fast, the subjects ate a standardized carbohydrate-rich breakfast. Whole saliva and blood were collected, and visual analogue scales for hunger and satiety were completed once before and continuously for 5 h after the breakfast. RESULTS: A lower pre- and postprandial whole saliva flow rate was found in subjects with bulimia nervosa, which might have been attributable to a concomitant intake of potentially xerogenic medication. Subjects with bulimia nervosa experienced reduced hunger, which could not be explained by pre- or postprandial alterations in circulating ghrelin, leptin, insulin, or glucose concentrations. CONCLUSIONS: There were no apparent differences in the composition of blood and saliva between bulimia nervosa and control subjects, and meal-induced compositional changes in blood were not directly mirrored in saliva composition.
|Presence of obestatin in breast milk: relationship among obestatin, ghrelin, and leptin in lactating women. |
Suleyman Aydin, Yusuf Ozkan, Fazilet Erman, Bilgin Gurates, Nermin Kilic, Ramis Colak, Tugba Gundogan, Zekiye Catak, Mahmut Bozkurt, Okhan Akin, Yasar Sen, Ibrahim Sahn
Nutrition (Burbank, Los Angeles County, Calif.) 24 689-93 2008
OBJECTIVE: The peptide hormones ghrelin and leptin have been found in blood and breast milk. This study was undertaken to investigate whether breast milk also contains obestatin, which is derived from the same gene as ghrelin but has opposite actions, and to characterize the relations among serum and milk ghrelin, obestatin, and leptin levels in lactating mothers. METHODS: Venous blood, colostrum, and mature milk were obtained from healthy lactating women (n = 31) just before suckling. The ghrelin and obestatin concentrations were determined by radioimmunoassay. Leptin levels were measured by enzyme-amplified sensitivity immunoassay. RESULTS: Obestatin levels in colostrum (538.9 pg/mL) and mature milk (528.5 pg/mL) were more than twice the corresponding blood levels (270.3 and 289.4 pg/mL, respectively). In contrast, leptin levels in colostrum (2.01 ng/mL) and mature milk (2.04 ng/mL) were more than five-fold lower than the corresponding blood levels (11.54 ng/mL). There was no correlation between breast milk ghrelin levels and leptin (r = -0.18, P > 0.05). However, there was a positive correlation between leptin levels in breast milk and blood (r = 0.369, P 0.05). CONCLUSION: The origin of milk obestatin is not currently known, but it comes from the blood or breast and may drain through the mammary glands into the milk. Ghrelin, obestatin, and leptin in the milk may directly affect appetite and their levels may be related to the regulation of energy balance and the pathogenesis of obesity.
|Simultaneous quantification of acylated and desacylated ghrelin in biological fluids. |
Suleyman Aydin,Fikret Karatas,Hikmet Geckil
Biomedical chromatography : BMC 22 2008
This study reports simultaneous quantification of both acylated and desacylated forms of ghrelin in biological samples, utilizing a reverse-phase high-performance liquid chromatography (HPLC) system. The HPLC assay was also compared with RIA assays in use. Biological samples (serum, saliva, urine, milk) known for the presence of ghrelin were collected from a total of eight post-partum women and eight male volunteers. Analysis of ghrelin with HPLC was also validated for linearity, precision, detection limit and accuracy. An elution time of 6 min was observed for pure (commercial) desacylated human ghrelin and for the same form of the hormone from all body fluids studied. The elution time for acylated pure human ghrelin and that in body fluids, however, was around 16 min. The mean recovery rate was over 90% for both forms with no significant interference. The lowest detectable levels for acylated and desacylated ghrelin with the method used here were 11 (+/-2) and 14 (+/-3) pg mL(-1), respectively. Given its simplicity, accuracy, time and cost-effectiveness, the HPLC method described here for determination of two forms of ghrelin (active and inactive) might prove useful for certain diagnostic purposes.
|Effects of glucose-to-fructose ratios in solutions on subjective satiety, food intake, and satiety hormones in young men. |
Tina Akhavan, G Harvey Anderson
The American journal of clinical nutrition 86 1354-63 2007
BACKGROUND: The greater prevalence of obesity and the metabolic syndrome in the past 35 y has been attributed to the replacement of sucrose in the food supply with high-fructose corn syrup (HFCS). OBJECTIVE: Two experiments were conducted to determine the effect of solutions containing sucrose, HFCS, or various ratios of glucose to fructose (G:F) on food intake (FI), average appetite (AA), blood glucose (BG), plasma insulin, ghrelin, and uric acid (UA) in men. DESIGN: Sugar solutions (300 kcal/300 mL) were (in %) G20:F80, HFCS 55 (G45:F55), sucrose, and G80:F20 (experiment 1, n = 12) and G20:F80, G35:F65, G50:F50, sucrose, and G80:F20 (experiment 2, n = 19). The controls were a sweet energy-free control (experiment 1) and water (both experiments). Solutions were provided in a repeated-measures design. AA, BG, and FI were measured in all subjects. Hormonal responses and UA were measured in 7 subjects in experiment 2. Measurements were taken from baseline to 75 min. FI was measured at 80 min. RESULTS: Sucrose and HFCS (experiment 1) and sucrose and G50:F50 (experiment 2) had similar effects on all dependent measures. All sugar solutions similarly reduced the AA area under the curve (AUC). FI and plasma UA concentrations were significantly (P 0.05) lower after high-glucose solutions than after low-glucose solutions. The lower FI was associated with a greater BG AUC (P 0.05) and smaller AA and ghrelin AUCs (P 0.01). Insulin and BG AUCs were positively associated (P 0.001). CONCLUSION: Sucrose, HFCS, and G50:F50 solutions do not differ significantly in their short-term effects on subjective and physiologic measures of satiety, UA, and FI at a subsequent meal.
|Gonadectomy and high dietary fat but not high dietary carbohydrate induce gains in body weight and fat of domestic cats. |
Robert C Backus, Nick J Cave, Duane H Keisler
The British journal of nutrition 98 641-50 2007
A high concentration of dietary carbohydrate is suggested to increase the risk of obesity and diabetes mellitus in domestic cats. To evaluate this, food intake, body weight, fat mass and circulating adiposity-related factors were determined in twenty-four sexually mature (9-12 months) cats assigned to four six-cat dietary groups balanced for body weight and sex. The effect of dietary fat in exchange for carbohydrate at 9, 25, 44 and 64 % of metabolisable energy (ME) in a purified diet of constant protein:ME ratio was studied 13 weeks before and 17 weeks after gonadectomy (GX). Body weight did not significantly change among the cats before GX except for an increase of 17 (sem 5) % in cats given the highest-fat diet. Following GX, all groups gained body weight, and body fat mass was positively correlated (r 0.50; P 0.04) with dietary fat percentage. Post-GX weight gains were much greater for females (+39 (sem 5) %) than males (+10 (sem 4) %). Plasma ghrelin concentration negatively correlated (P 0.02) with dietary fat percentage and, before GX, was greater (P 0.05) in females than males. Plasma insulin concentration increased with weight gain induced by high dietary fat. Plasma glucose, TAG and leptin concentrations were not affected by dietary fat percentage, GX or weight gain. These data provide evidence that in cats, high dietary fat, but not carbohydrate, induces weight gain and a congruent increase in insulin, while GX increases sensitivity to weight gain induced by dietary fat.
|Increase in ghrelin levels after weight loss in obese Zucker rats is prevented by gastric banding. |
Mariana P Monteiro, Andreia H Ribeiro, Ana F Nunes, Mónica M Sousa, J Duarte Monteiro, Artur P Aguas, M Helena Cardoso
Obesity surgery 17 1599-607 2007
BACKGROUND: Gastric banding is thought to decrease appetite in addition to the mechanical effects of food restriction, although this has been difficult to demonstrate in human studies. Our aim was to investigate the changes in orexigenic signals in the obese Zucker rat after gastric banding. METHODS: Obese Zucker rats (fa/fa) were submitted to gastric banding (GBP), sham gastric banding fed ad libitum (sham), or sham operation with food restriction, pair-fed to the gastric banding group (sham-PF). Lean Zucker rats (fa/+) were used as additional controls. Body weight and food intake were daily recorded for 21 days after surgery when epididymal fat was weighed and fasting ghrelin and hypothalamic NPY mRNA expression were measured. RESULTS: Gastric banding in obese Zucker rats resulted in a significant decrease of cumulative body weight gain and food intake. Furthermore, gastric banded rats were leaner than Sham-PF, as expressed by a significantly lower epididymal fat weight. Ghrelin levels of gastric banded rats were not increased when compared to sham-operated animals fed ad libitum and were significantly lower than the levels of weight matched sham-PF rats (1116.9 +/- 103.3 g GBP vs 963.2 +/- 54.3 g sham, 3,079.5 +/- 221.6 sham-PF and 2,969.9 +/- 150.9 g lean rats, p 0.001); hypothalamic NPY mRNA expression was not increased in GBP when compared to sham-operated rats. CONCLUSION: In obese Zucker rats, GBP prevents the increase in orexigenic signals that occur during caloric deprivation. Our data support the hypothesis that sustained weight loss observed after gastric banding does not depend solely on food restriction.
|Regulation of appetite in lean and obese adolescents after exercise: role of acylated and desacyl ghrelin. |
Kerry J Mackelvie, Graydon S Meneilly, Dariush Elahi, Alfred C K Wong, Susan I Barr, Jean-Pierre Chanoine
The Journal of clinical endocrinology and metabolism 92 648-54 2007
CONTEXT: Increased physical activity is an integral part of weight loss programs in adolescents. We hypothesized that exercise could affect appetite-regulating hormones and the subjective desire to eat, which could partly explain the poor success rate of the existing interventions. OBJECTIVE: The objective of this study was to investigate prospectively the effects of exercise on acylated ghrelin (AG) and desacyl ghrelin (DG) concentrations and on appetite. SETTING: The setting for this study was a tertiary care center. PARTICIPANTS: Normal-weight [NW; body mass index (mean +/- se), 20.7 +/- 0.5 kg/m2] and overweight (OW; body mass index, 32.4 +/- 1.7) male adolescents (n = 17/group, age 15.3 +/- 0.2 yr) were studied. INTERVENTION: Those studied participated in 5 consecutive days of aerobic exercise (1 h/d). MAIN OUTCOME: Changes in AG and DG concentrations and in appetite during a test meal were studied. RESULTS: Exercise did not significantly affect insulin sensitivity or body weight. Fasting total (AG and DG) ghrelin concentrations were lower in OW (600 +/- 33 pg/ml) compared with NW (764 +/- 33 pg/ml, P 0.05) boys and were not affected by exercise. In contrast, there was a differential effect of exercise on both AG and DG (P or= 0.019). AG significantly increased after exercise, and this increase was greater in NW compared with OW adolescents (P 0.05). Higher AG concentrations were correlated with an increase in markers of appetite (P 0.05). CONCLUSION: Exercise differentially affects AG and DG in NW and OW male adolescents. Our data suggest that total ghrelin does not adequately reflect AG and DG concentrations and that the influence of exercise-induced hormonal changes should be considered to ensure success in weight management.
|Influence of weight loss on plasma ghrelin responses to high-fat and high-carbohydrate test meals in obese women. |
Monique Romon, Séverine Gomila, Pascale Hincker, Bruno Soudan, Jean Dallongeville
The Journal of clinical endocrinology and metabolism 91 1034-41 2006
BACKGROUND: Diet-induced weight loss is associated with an increase in fasting ghrelin. The influence of weight loss on postprandial ghrelin response remains discussed, but the specific response to macronutrients is not known. OBJECTIVE: The objective of the study was to assess the influence of weight loss in obese women on the plasma ghrelin response to a fat- or carbohydrate-rich meal. DESIGN: Seventeen obese women (mean body mass index 37.6 +/- 5 kg/m2) were given an energy-restricted diet (800 kcal/d) for 7 wk, followed by a maintenance diet for 1 wk. Before and after the weight reduction diet, each woman was given (in random order) two isoenergetic test meals, corresponding to 40% of daily energy needs. The test meals contained either 80% fat and 20% protein or 80% carbohydrate and 20% protein. Blood samples were collected over a 10-h period. Two-way ANOVA with repeated measures was used to assess the effect of the test meal on variables. RESULTS: Weight loss (-11.2 +/- 1.4 kg) was associated with a significant decrease in baseline plasma insulin (9.7 +/- 4.1 to 7.9 +/- 2.4 mU/ml; P 0.0001) and leptin (25.9 +/- 8.3 to 17.2 +/- 7.8 ng/ml; P 0.0001) and an increase in plasma ghrelin (1.86 +/- 1.05 to 2.28 +/- 1.48 ng/ml; P 0.05). Before weight loss, there was no significant difference in postprandial ghrelin response between the test meals. After weight reduction, the ghrelin response was more pronounced after the carbohydrate test meal than after the fat test meal (P 0.02). CONCLUSION: Weight loss is associated with an improved postprandial plasma ghrelin response to a carbohydrate meal, whereas the response to a fat meal is not modified.
|Prenatal influences on leptin sensitivity and susceptibility to diet-induced obesity. |
Stefan O Krechowec, Mark Vickers, Arieh Gertler, Bernhard H Breier
The Journal of endocrinology 189 355-63 2006
Obesity and type 2 diabetes are world wide health issues and their incidence is rapidly increasing. Currently the biological factors responsible for the development of obesity are only partially understood. Recent research has shown that maternal nutrition during pregnancy may have long-term metabolic consequences in offspring. In the present study we investigated interactions between prenatal and postnatal nutrition on leptin sensitivity and obesity development. Wistar rats were time-mated and randomly assigned to either ad-libitum (AD) or to 30% of ad-libitum (UN) food intake throughout pregnancy. After weaning, female offspring were fed standard chow, a high-fat diet or a calorie restricted diet. Female offspring of UN dams were growth retarded at birth and showed increased susceptibility to diet-induced obesity on a high-fat diet. At 142 +/- 5 days of age, leptin sensitivity was measured as a response to 14 days of leptin treatment (2.5 microg/g/day, s.c.). In UN offspring fed chow, leptin treatment failed to reduce food intake and weight loss was diminished. This leptin resistance observed in UN offspring was independent of diet-induced obesity and was associated with fasting hyperinsulinemia and hypertriglyceridemia. Our study suggests that prenatal nutrition can shape future susceptibility to obesity through alterations in leptin sensitivity and changes in energy metabolism during adult life.
|Carob pulp preparation rich in insoluble dietary fiber and polyphenols enhances lipid oxidation and lowers postprandial acylated ghrelin in humans. |
Sindy Gruendel, Ada L Garcia, Baerbel Otto, Corinna Mueller, Jochen Steiniger, Martin O Weickert, Maria Speth, Norbert Katz, Corinna Koebnick
The Journal of nutrition 136 1533-8 2006
Ghrelin is an orexigenic hormone that may affect substrate utilization in humans. Ghrelin is influenced by macronutrients, but the effects of insoluble dietary fiber and polyphenols are unknown. We investigated the effects of a polyphenol-rich insoluble dietary fiber preparation from carob pulp (carob fiber) on postprandial ghrelin responses and substrate utilization. Dose-dependent effects of the consumption of carob fiber were investigated in a randomized, single-blind, crossover study in 20 healthy subjects, aged 22-62 y. Plasma total and acylated ghrelin, triglycerides, and serum insulin and nonesterified fatty acids (NEFA) levels were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal with 0, 5, 10, or 20 g of carob fiber over a 300-min period. The respiratory quotient (RQ) was determined after consumption of 0 or 20 g of carob fiber. Carob fiber intake lowered acylated ghrelin to 49.1%, triglycerides to 97.2%, and NEFA to 67.2% compared with the control meal (P 0.001). Total ghrelin and insulin concentrations were not affected by consumption of a carob fiber-enriched liquid meal. Postprandial energy expenditure was increased by 42.3% and RQ was reduced by 99.9% after a liquid meal with carob fiber compared with a control meal (P 0.001). We showed that the consumption of a carob pulp preparation, an insoluble dietary fiber rich in polyphenols, decreases postprandial responses of acylated ghrelin, triglycerides, and NEFA and alters RQ, suggesting a change toward increased fatty acid oxidation. These results indicate that carob fiber might exert beneficial effects in energy intake and body weight.
|Ghrelin gene expression is markedly higher in fetal pancreas compared with fetal stomach: effect of maternal fasting. |
Jean-Pierre Chanoine, Alfred C K Wong
Endocrinology 145 3813-20 2004
Ghrelin is an orexigenic peptide secreted mainly by the stomach in adult rats. Ghrelin concentrations increase with fasting and decrease after food intake. Ghrelin is also present in the placenta and in the fetal stomach, but the role of fetal ghrelin remains unclear. In this study, we compared changes in plasma ghrelin, insulin, and glucose concentrations and in ghrelin gene expression in stomach, pancreas, and placenta in response to fasting and feeding in adult nonpregnant rats and in 20-d pregnant dams and their fetuses. Plasma total ghrelin concentrations were three times higher in the fetus than in the dam but did not increase in response to fasting. In contrast to total ghrelin, plasma active ghrelin concentrations wee 50% lower in the fetus compared with the adult pregnant rat. Ghrelin mRNA and total ghrelin were markedly elevated in the fetal pancreas and six to seven times greater than in the fetal stomach but were not affected by fasting. In contrast, fetal pancreas and stomach active ghrelin concentrations increased two to three times after maternal fasting. Ghrelin receptor mRNA was present in all fetal pancreas samples. Placenta ghrelin gene expression was detectable but low. These data raise the possibility that in the fetus, in contrast to the adult, the pancreas and not the stomach is a major source of circulating immunoreactive ghrelin. Furthermore, the presence of a strong ghrelin gene expression and of ghrelin receptor mRNA in the fetal pancreas is intriguing and suggests that ghrelin may play an important role in beta-cell development.
|Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2. |
Stengel A, Goebel-Stengel M, Wang L, Shaikh A, Lambrecht NW, Rivier J, Taché Y
American journal of physiology Gastrointestinal and liver physiology 2001
Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst(2)) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P < 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin-O-acyltransferase protein concentrations, respectively (P < 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst(2a) receptor and the sst(2) agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst(2) antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst(2) receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus.
|What is the difference between active and total Ghrelin RIAs/ELISAs?||The active assays require the intact octanoyl group on the 3rd AA which means samples need to be acidified and treated with aprotinin, while total/desacyl assays can read the truncated form without the octanoyl modification.|
|QUALITY CONTROL RANGES: TOTAL GHRELIN RIA KIT|