The effect of macronutrients on appetite responses and meal induced thermogenesis in obesity

The theme of this Thesis is to understand the role of macronutrients on postprandial responses of gastrointestinal appetite hormones, meal induced thermogenesis (MIT) and satiety in obesity. A systematic review and meta-analysis (Chapter 2) in children revealed that the response of gut-derived appetite hormones to meal intake is different in obese compared with healthy weight children. Attenuated changes in ghrelin (orexigenic) and peptide YY (PYY) (anorexigenic) were observed at 60 mins (N=5 studies; n=129 participants (n=128 for PYY) (p<0.05) and 120 minutes postprandial (N=4; n=100, p<0.05) in obese children. A research gap identified from this review was the possible influence of meal composition on appetite responses, with some evidence indicating the potential for specific macronutrient effects on gut hormone response to enhance endogenous sensitivity in children. In light of the attenuated hormone response in obese children observed from the meta-analysis, this is an area worthy of investigation. As both protein and carbohydrate have widely reported roles in appetite regulation, two parallel randomised double blinded postprandial cross over studies were undertaken to examine the effects of a high protein and high carbohydrate meal on ghrelin, PYY and glucagon-like peptide-1(GLP-1) (Chapter 4) and MIT (Chapter 5). Similar to the findings from the meta-analysis, obese compared with healthy weight children had lower fasting ghrelin (p=0.001) and an attenuated ghrelin response after meal intake (incremental area under the curve (iAUC), -25,896.5 ± 7943 pg/mL/4hr vs. -60,863.5 ± 13104 pg/mL/4hr, p=0.008), which was irrespective of meal composition. When change in ghrelin was assessed over time, the high protein compared with the high carbohydrate meal resulted in a ghrelin response indicative of enhanced satiety in both obese and normal weight children (p=0.018). Neither meal type however had any influence on GLP-1 or PYY regardless of weight status. In addition, consumption of a high protein compared with a high carbohydrate meal, resulted in greater MIT (iAUC 258.4 ± 18.4 kJ/4hr vs 136.3 ± 11.3 kJ/4hr, p<0.001) and fat oxidation (iAUC 2.2 ± 0.5 g/4hr vs -4.7 ± 0.6 g/4hr, p<0.001) similarly in both obese (n=13) and healthy weight (n=13) children (p>0.05). As well as eliciting a greater MIT, a high protein compared to a high carbohydrate meal was observed to promote greater self-perceived fullness (AUC 13157 ± 1073 mm/4hr vs 11824 ± 1013 mm/4hr, (p=0.012), which was not different between the obese (n=17) and healthy weight (n=24) children (Chapter 6). Taken together, these studies indicate a definite role for protein in the modulation of energy balance by impacting favourably on ghrelin secretion, increasing energy expenditure through increased MIT and satiety. In light of the influence of macronutrient composition on energy expenditure, the MIT associated with different fatty acids in adults was investigated. Recent evidence points to differences in the metabolic handling of dietary fats based on chain length and saturation. Chapter 7 reports a three-way single blinded crossover study in overweight/obese adults (n=13) comparing meals high in either short-medium chain saturated fats, long chain saturated fats or monounsaturated fats on MIT. In contrast to the study hypothesis, MIT was not found to be markedly different after consumption of meals differing in fatty acid saturation and chain length. This Thesis has demonstrated that obesity in children is characterised by altered meal-induced gut-derived appetite hormone responses. Through manipulation of meal macronutrient composition, small changes in appetite hormone signalling, self-perceived satiety and meal-induced energy expenditure can be achieved in children. More research is required to understand the metabolic handling of different fat types before any conclusions can be ascertained in regards to their potential role in energy expenditure in adults. These findings make a unique and important contribution to the scientific evidence base on which to develop dietary strategies to assist in the regulation of energy balance in obesity.

Author requested conversion to open access 31 Oct 2022