Higher Fasting Ghrelin Research Articles

Associations between ghrelin and leptin and neural food cue reactivity in a fasted and sated state

Food cue exposure can trigger eating. Food cue reactivity (FCR) is a conditioned response to food cues and includes physiological responses and activation of reward-related brain areas. FCR can be affected by hunger and weight status. The appetite-regulating hormones ghrelin and leptin play a pivotal role in homeostatic as well as hedonic eating. We examined the association between ghrelin and leptin levels and neural FCR in the fasted and sated state and the association between meal-induced changes in ghrelin and neural FCR, and in how far these associations are related to BMI and HOMA-IR. Data from 109 participants from three European centers (age 50±18 y, BMI 27±5 kg/m2) who performed a food viewing task during fMRI after an overnight fast and after a standardized meal were analyzed. Blood samples were drawn prior to the viewing task in which high-caloric, low-caloric and non-food images were shown. Fasting ghrelin was positively associated with neural FCR in the inferior and superior occipital gyrus in the fasted state. This was partly attributable to BMI and HOMA-IR. These brain regions are involved in visual attention, suggesting that individuals with higher fasting ghrelin have heightened attention to food cues. Leptin was positively associated with high calorie FCR in the medial prefrontal cortex (PFC) in the fasted state and to neural FCR in the left supramarginal gyrus in the fasted versus sated state, when correcting for BMI and HOMA-IR, respectively. This PFC region is involved in assessing anticipated reward value, suggesting that for individuals with higher leptin levels high-caloric foods are more salient than low-caloric foods, but foods in general are not more salient than non-foods. There were no associations between ghrelin and leptin and neural FCR in the sated state, nor between meal-induced changes in ghrelin and neural FCR. In conclusion, we show modest associations between ghrelin and leptin and neural FCR in a relatively large sample of European adults with a broad age and BMI range. Our findings indicate that people with higher leptin levels for their weight status and people with higher ghrelin levels may be more attracted to high caloric foods when hungry. The results of the present study form a foundation for future studies to test whether food intake and (changes in) weight status can be predicted by the association between (mainly fasting) ghrelin and leptin levels and neural FCR.

Pre-operative Predictors of Weight Loss and Weight Regain Following Roux-en-Y Gastric Bypass Surgery: a Prospective Human Study.

There are currently few pre-operative predictors of initial and long-term weight loss following bariatric surgery. We evaluated the role of pre-operative patient characteristics and baseline gut and adipose-derived hormones in predicting maximal total body weight loss (WLmax) and risk of weight regain (WR) after Roux-en-Y gastric bypass (RYGB) surgery. One hundred five adult patients undergoing primary RYGB were prospectively recruited. Baseline demographics were recorded and fasting plasma glucose, glycosylated hemoglobin (A1C), insulin, glucagon, leptin, active ghrelin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured on day of surgery. Our cohort had a mean age of 44.4 ± 13.0years, and initial BMI (body mass index) of 45.1 ± 6.7kg/m2 with mean post-operative follow-up of 40months. Eighty patients were female and 26 had type 2 diabetes mellitus (T2D). Average WLmax was 35.3 ± 7.4%. On univariate analysis, higher baseline fasting ghrelin, lower age, lower CRP (C-reactive protein), lower A1C, and negative T2D status were associated with greater WLmax (p < 0.05). Controlling for these variables using stepwise multivariate regression, only higher fasting ghrelin and younger age were associated significantly with greater WLmax (p < 0.05). In subgroup multivariate regression analysis of T2D patients, higher ghrelin and glucagon were significantly associated with greater WLmax. Following stepwise multivariate regression, lower initial BMI and lower glucagon were associated with greater WR (p < 0.05). Incorporation of baseline biological and hormonal markers may help in developing more accurate predictive models for weight loss following bariatric surgery that help inform patient counseling and decision-making.

Developmental stage-dependent relationships between ghrelin levels and hippocampal white matter connections in low-weight anorexia nervosa and atypical anorexia nervosa

IntroductionDisruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown. MethodsWe evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20). ResultsFA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty. ConclusionsIn post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.

Changes in appetite-regulating hormones following food intake are associated with changes in reported appetite and a measure of hedonic eating in girls and young women with anorexia nervosa

BackgroundFemales with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN. ObjectiveTo examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls. Methods68 females (36 AN, 32 controls) 10–22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 min following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 min after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 h after breakfast. ResultsAN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 min), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p < 0.0001). In AN (particularly AN-restrictive subtype), BDNF AUC was positively associated with kilocalories consumed during the CTT ConclusionsIn young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN.

Higher fasting ghrelin serum levels in active smokers than in former and never-smokers

Objectives Ghrelin, an orexigenic peptide hormone, promotes drug reward and is suspected to play a role in nicotine dependence. However, there is little data on whether ghrelin levels are associated with active and/or former smoking. The relationship between ghrelin serum levels and smoking status in a population-based sample of individuals was studied. Methods Total ghrelin was determined after an overnight fast in 1519 subjects participating in a population-based cohort study (‘LIFE-Adult’). Tobacco consumption was assessed using both the questionnaire and interview. Generalised linear models with gamma distribution and log-link function were performed to analyse the association of total serum ghrelin with smoking status and the association between serum ghrelin and the amount of tobacco consumed in active smokers. Results Ghrelin levels were positively associated with active, but not former smoking (OR = 1.095; p = .002). This association was not moderated by sex (interaction of ‘active smoking’ and sex: p = .346). Ghrelin levels were not associated with the amount of tobacco consumed in active smokers. Conclusions This study provides evidence that total ghrelin serum levels are positively associated with active smoking. No association was found for former smokers. A unique feature of the study is the large sample size.

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome.

The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs). In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.

Multi‐Vitamin Supplementation during Pregnancy in Rats Alters the Development of Food Intake Regulation in the Offspring

Multi-vitamin supplements are commonly consumed by women, especially during pregnancy. Increased vitamin intake during pregnancy may alter the expression of genes regulating metabolic systems in the offspring. Thus, we tested the effect of high multi-vitamin intake during pregnancy in rats on food intake (FI) regulation and body weight in the offspring. Two groups of pregnant Wistar rats were fed the AIN-93 diet containing either the recommended (RV) or 10X higher vitamin (HV) content by addition of the AIN vitamin mix. In male pups (n=10/group), body weight (g) and daily FI (g/day) were measured weekly from birth. Also, 1 hr FI was measured 30 min after the pups received either a glucose (5 g/kg) or water preload given by gavage in random order and on alternate days after an overnight fast. Plasma ghrelin and GLP-1 were measured at weaning and 15 wks. Compared to RV offspring, HV offspring were not different in birth weight, but were 5% lighter at weaning (P<0.05) and 6% heavier at 15 wks (P<0.01). At weaning, HV offspring had 32% higher fasting GLP-1 (P<0.01) and a 150% greater decrease in FI (P<0.01) after the glucose load compared to RV offspring. However, at 15 wks, HV offspring compared to RV offspring ate 10% more throughout the day (P<0.05), had 24% higher fasting ghrelin (P<0.01), a 29% lower GLP-1 response (P<0.01) and failed to suppress FI after the glucose preload (−3.1 ± 0.4 vs. −4.1 ± 0.5 g; P<0.05). In conclusion, HV intake during pregnancy in rats alters the development of food intake regulation in the offspring. Supported by CIHR-INMD.