Abstract
Nutrition strategies offer a widely available approach to managing conditions such as overweight/obesity and type 2 diabetes (T2D). It is widely established that different dietary nutrients are capable of stimulating gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY), which act to improve blood glucose regulation and/or reduce appetite. Despite this, the half-life of GLP-1 is remarkably short, in part due to the enzyme dipeptidyl-peptidase-IV (DPP4) which rapidly cleaves GLP-1 reducing its availability for receptor binding. Recent evidence suggests that protein and calcium act synergistically to further enhance the availability of these hormones. The aim of this thesis was first to examine the conditions which mediate this relationship, in both lean and overweight/obese populations; and second, to determine whether GLP-1 secretion differs in T2D and the population specific effects of DPP4 on GLP-1 activation status and action.In Chapter 4, increasing doses of calcium co-ingested with whey protein hydrolysate did not augment GLP-1 concentrations in individuals with overweight/obesity. Furthermore, postprandial GLP-1 was not different following the ingestion of protein alone versus the co-ingestion of protein with calcium. The findings of this study suggested that a high protein dose may be important, or that the synergistic effect of protein and calcium may not exist in an overweight/obese population. In Chapter 5, GLP-1 concentrations were accentuated following the co-ingestion of calcium with a novel aggregate protein, but not with a whey protein isolate. This was not apparent for PYY concentrations. Gastric emptying rate slowed with the presence of calcium and energy intake was greater following the ingestion of whey protein compared to the aggregate protein. These findings suggest that the form of protein upon entering the intestine could be important for delaying absorption and enhancing release of gut hormones. In Chapter 6, DPP4 activity was greater in the overweight/obese groups compared to the lean group, although this did not correlate with changes in appetite. Although, DPP4 release from adipose tissue explants was greater from samples collected from the lean group, except when scaled for whole-body fat mass where DPP4 release was greater in obese versus lean groups. Exercise (in absence of weight loss) did not alter DPP4 activity/ concentrations, which suggested that weight loss, but not improvement in fat regulation, is important for reducing DPP4 activity/concentrations. Lastly, in Chapter 7, a systematic review and meta-analyses suggested that fasting GLP-1 and postprandial GLP-1 secretion is not different between individuals with and without T2D. There was large heterogeneity between studies which may help to explain the inconsistent findings in the literature. Furthermore, the assay type employed was found to influence the overall effect size, which highlights the difficulties surrounding GLP-1 measurement and the importance of careful consideration of assay type.
This thesis has shown that the co-ingestion of protein and calcium does not consistently augment gut hormone release. Feeding a high protein dose and/or delaying nutrient absorption may be important requirements for a combined effect of protein and calcium on gut hormone release. DPP4 activity was greater in individuals with overweight/obesity, although this does not appear to correlate with appetite sensations. Lastly, GLP-1 secretion is not different between individuals with and without T2D.
Key words: protein, calcium, appetite, energy intake, gut hormones.
| Date of Award | 27 Apr 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Javier Gonzalez (Supervisor), Francoise Koumanov (Supervisor) & James Betts (Supervisor) |