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Title: Effect of exercise and common obesity single nucleotide polymorphisms on appetite and appetite-regulatory hormones
Author: Dorling, James L.
ISNI:       0000 0004 7970 9812
Awarding Body: Loughborough University
Current Institution: Loughborough University
Date of Award: 2017
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Over the last decade, the fat mass and obesity associated gene (FTO) rs9939609 variant and gastrin-releasing peptide gene (GRP) rs7243357 variant have been identified as obesity susceptibility polymorphisms. Evidence from humans indicates that the former of these loci modulates obesity risk through alterations in food intake, which could be related to differences in the hunger hormone ghrelin. No studies have examined the mechanisms underlying the link between obesity and the GRP rs7243357 variant, although it is possible this polymorphism is related to disparities in the encoded satiety signal gastrin-releasing peptide. These gene-appetite relationships suggest that risk allele carriers at these polymorphisms may benefit from therapeutic interventions that target appetite and appetite hormone systems. In this regard, a single bout of high-intensity exercise transiently suppresses appetite without causing compensatory elevations in energy intake in the hours afterwards. Evidence suggests such bouts also change plasma concentrations of episodic appetite hormones in a direction consistent with the acute reduction in subjective appetite. Nevertheless, it is not known if these responses are modulated by different genotypes at the FTO rs9939609 and GRP rs7243357 loci. Thus, the aim of the present thesis was to investigate the effect of an acute bout of exercise on appetite and appetite-regulatory hormones in variants of the FTO rs9939609 and GRP rs7243357 single nucleotide polymorphisms. A total of 361 males were recruited to a database in Chapter 4. FTO rs9939609 and GRP rs7243357 genotype were determined, further to anthropometric traits, eating behaviour and levels of physical activity. As part of an exploratory analysis, Chapter 4 showed that the FTO rs9939609 and GRP rs7243357 genotypes were not linked to anthropometric traits or eating behaviours within the cohort of physically active males who partook. In Chapter 5, a cohort of 12 'obesity-risk' AA and 12 TT subjects at the FTO rs9939609 locus were recruited from the database for an acute exercise intervention study consisting of two trials: exercise and control. Individuals with the AA genotype displayed greater postprandial acylated ghrelin, subjective appetite and energy intake compared to TTs in the control trial. Exercise caused a greater suppression of acylated ghrelin in AAs, negating differences seen in the control trial. However, the suppression of appetite during exercise and the lack of compensatory changes in appetite and energy intake after exercise were similar between AAs and TTs. Chapter 6 reports a similar acute exercise intervention study performed in 'obesity-risk' TTs and GGs of the GRP rs7243357 variant. Exercise provoked a greater increase in plasma concentrations of GRP in TTs compared to GGs that nullified lower GRP levels seen in TTs in the control trial. There were no differences between TTs and GGs in appetite and energy intake in either trial, although exercise did acutely suppress appetite perceptions and did not cause elevations in appetite and energy intake in the hours after exercise. In the main, results from this thesis suggest that both the studied SNPs were linked to postprandial variations in appetite-regulatory peptides in the control trial, though only the FTO rs9939609 loci was linked to differences in appetite and energy intake. A single bout of acute exercise adjusts levels of appetite hormones in a direction accordant to the concomitant reduction in appetite, and may negate hormonal dissimilarities observed between genotypes at rest. Crucially, however, all homozygous groups from Chapters 5 and 6 showed comparable reductions in appetite during exercise and did not atone for the exercise-induced energy deficit through increases in appetite or energy intake in the hours after exercise. Therefore, despite the need for further work into the genetic variability in appetite hormone responses to exercise, the current thesis suggests exercise should continue as a universal method of provoking a transient calorie deficit.
Supervisor: Not available Sponsor: Loughborough University
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medical and Health Sciences not elsewhere classified ; Obesity ; Fat-mass and obesity-associated gene ; Gastrin-releasing peptide gene ; Exercise ; Appetite ; Energy intake ; Energy balance ; Acylated ghrelin ; Gastrin-releasing peptide