Foods for appetite control: Can carbohydrates stimulate the ileal brake and enhance satiety?

New therapeutic approaches targeting appetite suppression for the management of body weight and prevention of obesity are currently of widespread interest. The research within this thesis has focused on the ileal brake, which is an endogenous appetite suppression mechanism that is activated by the presence of macronutrients in the ileum. The aim of the thesis was to investigate whether this mechanism can be activated firstly by direct delivery of glucose, and if so, secondly through oral delivery of protected available carbohydrate (CHO) from foods into the ileum. If resulting in suppression of appetite and food intake, it was anticipated that the findings in this thesis may have important implications for the development of food-derived appetite suppressants and/or therapeutics. The first clinical trial (Chapter 4) in this thesis used a model in which 14 healthy male volunteers were intubated with a 3.8 m long naso-ileal (NI) tube, the aim of which was to deliver glucose directly to the ileum, the distal small intestine (SI). The trial was a 5-day, randomised, residential, cross-over design investigating delivery of glucose (15 g) and saline to both the ileum and the duodenum. In this carefully controlled NI tube feeding study, there was evidence that the direct delivery of glucose into the ileum enhanced aspects of subjectively-rated satiety,glucagon-like-peptide-1 (GLP-1) and peptide YY (PYY) release, and decreased short-term energy intake (EI) compared with the direct delivery of saline into the ileum (-10%, -481 kJ, trend) and glucose into the duodenum (-22%, -988 kJ, Tukey???s post-hoc, P < 0.05) at an ad libitum lunch meal. An in vitro study (Chapter 5) was conducted to investigate the mechanisms by which intestinal enteroendocrine L-cells in the ileum couple glucose sensing to GLP-1 secretion using NCI-H716 cells, a human L-cell line model. The findings that GLP-1 secretion was triggered by glucose and inhibited by a well-established sGLT-1inhibitor and the presence of sGLT-1 transcript in the NCI-H716 cells suggest that the action of sGLT-1 is involved in glucose sensing. The findings that GLP-1 secretion was triggered by fructose and the presence of TAS1R2 receptor and ??-gustducin transcripts also suggest that the activation of sweet taste receptors may participate in the regulation of the secretion of GLP-1. In light of these results, it is possible to infer that glucose-induced GLP-1 secretion from L-cells in the ileum is a consequence of the combined effect of sGLT-1 and activation of the sweet taste receptors. The aim of the second clinical trial (Chapter 6) was to compare the effects of low-dose (500 mg) and high-dose (1500 mg) commercially available grape seed extract (GSE), hypothesised to induce post-meal CHO malabsorption in the proximal SI with a placebo control, consumed at the same time as a standardised high-starch breakfast meal on appetite over the subsequent 3-4 hours and EI at a subsequent ad libitum lunch meal in 20 healthy males. The trial was a randomised, double blind, placebo…