Gastrointestinal Sensing of Meal-Related Signals in Humans, and Dysregulations in Eating-Related Disorders

Abstract

The upper gastrointestinal (GI) tract plays a critical role in sensing the arrival of a meal, including its volume as well as nutrient and non-nutrient contents. The presence of the meal in the stomach generates a mechanical distension signal, and, as gastric emptying progresses, nutrients increasingly interact with receptors on enteroendocrine cells, triggering the release of gut hormones, with lipid and protein being particularly potent. Collectively, these signals are transmitted to the brain to regulate appetite and energy intake, or in a feedback loop relayed back to the upper GI tract to further adjust GI functions, including gastric emptying. The research in this area to date has provided important insights into how sensing of intraluminal meal-related stimuli acutely regulates appetite and energy intake in humans. However, disturbances in the detection of these stimuli have been described in a number of eating-related disorders. This paper will review the GI sensing of meal-related stimuli and the relationship with appetite and energy intake, and examine changes in GI responses to luminal stimuli in obesity, functional dyspepsia and anorexia of ageing, as examples of eating-related disorders. A much better understanding of the mechanisms underlying these dysregulations is still required to assist in the development of effective management and treatment strategies in the future.

The metabolic impact of small intestinal nutrient sensing

“…In support of a pre-absorptive lipid-sensing mechanism, intravenous infusion of Intralipid does not suppress food intake 28 , and the effects of duodenal Intralipid and/or linoleic acid occur independently of changes in circulating triglycerides 29 , 30 . Further, co-infusion of lipid with a lipase inhibitor blocks the ability of lipid to suppress food intake, as well as increase CCK and GLP-1 31 . However, the term “pre-absorptive lipid sensing” might be misleading as evidence suggests that the ability of intestinal lipid sensing to induce gut peptide release, activate vagal afferents, and reduce food intake is also dependent on chylomicron formation from LCFA and subsequent absorption to the basolateral side 32 – 34 .…”

Food, Eating, and the Gastrointestinal Tract

“…It is plausible that intraluminal and post-absorptive mechanisms are behind the effects of meal composition on postprandial sensations. The influence of meal composition and meal-related signals on digestive function and perception has been specifically addressed in another paper of this Special Issue [73].…”

Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes — impacts on gastric emptying, glucoregulatory hormones and glucose absorption

“…For example, in T2D, whey protein, when given as a preload 30 min before a high-carbohydrate meal, slowed gastric emptying and stimulated insulin, leading to a reduction in the glycaemic response 6 . These effects of protein appear to be mediated, at least in part, by their digestion products, amino acidsboth circulating amino acids and as a result of the interaction of amino acids with the small intestine [7][8][9][10] .…”