How and why do gastrointestinal peptides influence food intake?

Abstract

Despite the ability of some gastrointestinal hormones to reliably reduce meal size when administered prior to a meal, it is not understood why the repeated administration or genetic knockout of these hormones appear largely ineffective in reducing food intake and body weight. Here, we review evidence that the ability of GI peptides such as cholecystokinin (CCK) to elicit satiation is a consequence of prior learning. Evidence includes first, that the ability of some of these signals to modify food intake depends upon past experience and is malleable with new experience. Additionally, the ability of CCK and other gut signals to reduce food intake may not be hard-wired; i.e., any so-called "satiation" signal that reduces food intake in a single-meal situation may not continue to do so over repeated trials. The individual will respond to the signal only so long as it provides reliable information about caloric content. If a particular signal becomes unreliable, the individual will rely on other signals to end meals. Thus, gut peptides/hormones have important metabolic effects such as mediating absorption, digestion, and many aspects of the distribution of ingested nutrients throughout the body; and, if they have been reliably associated with natural stimuli that mediate satiation, they also inform behavior.

Figure 1

Control of meal size. As depicted in the upper left rectangle, meal size is thought to be controlled by a homeostatic negative-feedback loop. During a meal, food enters the gastrointestinal (GI) tract initiating multiple metabolic effects including digestion and absorption of nutrients. Some (as yet unknown) consequences of the metabolic activities is sensed and the signal is conveyed to the brain and elicits satiation or fullness. The current hypothesis is that the increase of GI peptides/hormones secreted as the food is being processed provides the signal that is sensed and elicits satiation; and the most studied of these hormones is CCK. When any of these hormones such as CCK is administered exogenously as a meal begins, it causes eating to stop prematurely, as depicted in the upper right.

Figure 2

Pavlovian Influence over Meal-Related Behaviors. Top panel: Food on the tongue, as occurs during meals, unconditionally elicits salivation. Food on the tongue is the unconditioned stimulus (US) and salivation is the unconditioned response (UR). When the UR to US reflex is reliably associated with another stimulus, one that does not normally elicit salivation such as a bell, the bell can develop the ability to elicit salivation without the necessity of food on the tongue; i.e., the bell becomes a conditioned stimulus (CS) and the salivation it elicits is a conditioned response (CR). Bottom panel: Analogous to the association between the bell and salivation in the top panel, gastrointestinal hormones such as CCK, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), amylin and apolipoprotein A-IV, that are secreted during meals can become associated with meal-elicited satiation. Thus, these hormones can be considered as CSs that elicit premature satiation (CR).