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-

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subject 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.