Interindividual variability in perceived appetite and appetite-related hormone responses to eating and exercise in humans

As obesity rates continue to rise worldwide, scientific interest in the area of appetite regulation has increased in an attempt to identify strategies that can prevent energy overconsumption and body weight gain. Appetite regulation is complex and involves many different physiological and psychological factors, allowing for great interindividual variability. Recently, some studies assessing appetite and energy intake responses to meal or exercise interventions have shifted the focus on presenting findings exclusively as group means to assessing individual responses and exploring interindividual variability. However, important methodological limitations may have impaired the detection of true interindividual variability, and gold standard study design and statistical approaches that address these limitations have been recently suggested. Therefore, this thesis aimed to assess the reproducibility and quantify the interindividual variability in appetite responses to acute exercise and to a standardised meal, and to explore the influence of genetic, physiological and behavioural characteristics on fasting and postprandial appetite-related outcomes. To achieve this, a total of 145 healthy men and women were recruited into four experimental studies.The first experimental study (Chapter 4) demonstrated, using a replicated crossover design, that young men exhibited reproducible appetite responses after 60-min of fasted treadmill running at 70% peak oxygen uptake. True interindividual variability was observed in acylated ghrelin, total peptide YY (PYY) and perceived appetite responses over and above any random within-subject variability and measurement error, even after adjustment for individual baseline measurements. In the second experimental study (Chapter 5), the fat mass and obesity- associated gene (FTO) was not significantly associated with fasting or postprandial perceived appetite, acylated ghrelin, total PYY, insulin, glucose and leptin in healthy men and women, with or without the addition of physiological and behavioural covariates in the statistical models. While fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes, the associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were small. The third experimental study (Chapter 6) employed a replicated crossover design to demonstrate that the reproducibility of appetite responses to a standardised meal (5025 kJ) is generally good in healthy men. True interindividual variability was present in perceived appetite, acylated ghrelin, total PYY, insulin and glucose responses to the meal beyond any random within-isubject variation over time, but the magnitude of change in postprandial appetite responses was not influenced by the FTO gene. The final experimental study (Chapter 7) consisted of a pilot study which showed no significant association between brown adipose tissue activity assessed with thermal imaging, FTO genotype and fasting and postprandial acylated ghrelin, total PYY, insulin and glucose in healthy males.Collectively, these studies demonstrate that appetite responses to acute exercise and to eating are reproducible in healthy men, and true interindividual variability exist in these responses. However, the FTO genotype was not significantly associated with fasting and postprandial perceived appetite and appetite-related hormones, and further studies are warranted to investigate other individual characteristics that may moderate the observed interindividual variability. These findings highlight the importance of exploring individual differences in appetite responses in the context of the prevention and/or management of obesity.</div

Interindividual responses of appetite to acute exercise: a replicated crossover study

This is an Open Access Article. It is published by Lippincott, Williams & Wilkins under the Creative Commons Attribution-NonCommercial 3.0 Unported Licence (CC BY-NC). Full details of this licence are available at: http://creativecommons.org/licenses/by-nc/4.0/Purpose: Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Methods: Fifteen healthy, recreationally-active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomised sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Inter-individual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition interactions. Results: Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62 to 1.47, P < 0.001), and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the SD of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54 to 0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-by-condition interactions were present for all variables (P ≤ 0.053). Conclusion: Our replicated cross-over study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time

Strength Training Prior to Endurance Exercise: Impact on the Neuromuscular System, Endurance Performance and Cardiorespiratory Responses

This study aimed to investigate the acute effects of two strength-training protocols on the neuromuscular and cardiorespiratory responses during endurance exercise. Thirteen young males (23.2 ± 1.6 years old) participated in this study. The hypertrophic strength-training protocol was composed of 6 sets of 8 squats at 75% of maximal dynamic strength. The plyometric strength-training protocol was composed of 6 sets of 8 jumps performed with the body weight as the workload. Endurance exercise was performed on a cycle ergometer at a power corresponding to the second ventilatory threshold until exhaustion. Before and after each protocol, a maximal voluntary contraction was performed, and the rate of force development and electromyographic parameters were assessed. After the hypertrophic strength-training and plyometric strength-training protocol, significant decreases were observed in the maximal voluntary contraction and rate of force development, whereas no changes were observed in the electromyographic parameters. Oxygen uptake and a heart rate during endurance exercise were not significantly different among the protocols. However, the time-to-exhaustion was significantly higher during endurance exercise alone than when performed after hypertrophic strength-training or plyometric strength-training (p <0.05). These results suggest that endurance performance may be impaired when preceded by strength-training, with no oxygen uptake or heart rate changes during the exercise

Interindividual responses of appetite to acute exercise: a replicated crossover study

Purpose: Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Methods: Fifteen healthy, recreationally-active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomised sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Inter-individual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition interactions. Results: Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62 to 1.47, P < 0.001), and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the SD of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54 to 0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-by-condition interactions were present for all variables (P ≤ 0.053). Conclusion: Our replicated cross-over study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time

Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women

Background: The fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite. Objectives: To explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women. Design: 112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics. Results: 95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (P ≥ 0.28) and postprandial (P ≥ 0.19) appetite-related outcomes. Eta2 values for explained variance attributable to FTO rs9939609 were &lt;5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (r = −0.23 to 0.15, P ≥ 0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (r = 0.29 to 0.81, P ≤ 0.033). Conclusions: Associations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women

Influence of short-term hyperenergetic, high-fat feeding on appetite, appetite-related hormones, and food reward in healthy men

Short-term overfeeding may provoke compensatory appetite responses to correct the energy surplus. However, the initial time-course of appetite, appetite-related hormone, and reward-related responses to hyperenergetic, high-fat diets (HE-HFD) are poorly characterised. Twelve young healthy men consumed a HE-HFD (+50% energy, 65% fat) or control diet (36% fat) for seven days in a randomised crossover design. Mean appetite perceptions were determined during an oral glucose tolerance test (OGTT) before and after each diet. Fasted appetite perceptions, appetite-related hormones, and reward parameters were measured pre-diet and after 1-, 3- and 7-days of each diet. The HE-HFD induced a pre-to-post diet suppression in mean appetite during the OGTT (all ratings p ≤ 0.058, effect size (d) ≥ 0.31), and reduced the preference for high-fat vs. low-fat foods (main effect diet p = 0.036, d = 0.32). Fasted leptin was higher in the HE-HFD than control diet (main effect diet p < 0.001, d = 0.30), whilst a diet-by-time interaction (p = 0.036) revealed fasted acylated ghrelin was reduced after 1-, 3- and 7-days of the HE-HFD (all p ≤ 0.040, d ≥ 0.50 vs. pre-diet). Appetite perceptions and total peptide YY in the fasted state exhibited similar temporal patterns between the diets (diet-by-time interaction p ≥ 0.077). Seven days of high-fat overfeeding provokes modest compensatory changes in subjective, hormonal, and reward-related appetite parameters

No influence of the fat mass and obesity-associated gene rs9939609 single nucleotide polymorphism on blood lipids in young males

The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations

True interindividual variability exists in postprandial appetite responses in healthy men but is not moderated by the FTO genotype

Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives: This study aimed to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD 28.5 ± 9.8 years, 27.0 ± 5.0 kg·m-2 ) recruited according to FTO genotype (9 AA, 9 TT) completed two identical control and two identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson’s product-moment correlations between the first and second replicate of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated ghrelin and appetite perceptions (standardized effect sizes (ES): 0.18-4.26) and elevated total PYY, insulin and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal versus control conditions. Moderate-to-large positive correlations were observed between the two replicates of control-adjusted meal responses for all variables (r=0.44-0.86, P≤0.070). Participant-by-condition interactions were present for all variables (P≤0.056). FTO genotype-by-condition interactions were not significant (P≥0.19) and treatment effect differences between genotype groups were small (ES≤0.27) for all appetite parameters. Conclusions: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but is not moderated by the FTO genotype. These findings highlight the 3 importance of exploring individual differences in appetite for the prevention and/or treatment of obesity. Clinical trial registry number: NCT03771690 (ClinicalTrials.gov)

Individual variation in hunger, energy intake and ghrelin responses to acute exercise

Purpose: To characterise the immediate and extended impact of acute exercise on hunger, energy intake and circulating acylated ghrelin concentrations using a large dataset of homogenous experimental trials; and to describe the variation in responses between individuals. Methods: Data from 17 of our group’s experimental crossover trials were aggregated yielding a total sample of 192 young, healthy, males. In these studies, single bouts of moderate to high-intensity aerobic exercise (69 ± 5% VO2 peak; mean ± SD) were completed with detailed participant assessments occurring during and for several hours post-exercise. Mean hunger ratings were determined during (n = 178) and after (n = 118) exercise from visual analogue scales completed at 30 min intervals whilst ad libitum energy intake was measured within the first hour after exercise (n = 60) and at multiple meals (n = 128) during the remainder of trials. Venous concentrations of acylated ghrelin were determined at strategic time points during (n = 118) and after (n = 89) exercise. Results: At group-level, exercise transiently suppressed hunger (P < 0.010; Cohen’s d = 0.77) but did not affect energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001; Cohen’s d = 0.10) and remained significantly lower than control (no exercise) afterwards (P < 0.024; Cohen’s d = 0.61). Between participants, there were notable differences in responses however a large proportion of this spread lay within the boundaries of normal variation associated with biological and technical assessment error. Conclusion: In young men, acute exercise suppresses hunger and circulating acylated ghrelin concentrations with notable diversity between individuals. Care must be taken to distinguish true inter-individual variation from random differences within normal limits