The control of food intake: behavioral versus molecular perspectives

Abstract

To meet the continuous demand for energy, organisms use diverse signals to match food intake with energy needs. This paper reviews the effect of satiation signals and adiposity signals on food intake, including how they interact in the brain and how their influence changes with experience. Whereas meal initiation is influenced by external environmental factors, meal size is influenced by an array of signals that can be partitioned according to their reliability in indicating caloric content of food. It is argued that the malleability of satiation signals renders them poor candidates as pharmacological targets to control body weight.

Figure 1. Physiology of Satiation

Several categories of signals converge on the brain to influence energy homeostasis. Satiation signals such as CCK and GLP-1 arise from the gastrointestinal tract and related organs during meals and are conveyed to the hindbrain. Adiposity signals are hormones whose secretion is proportional to body fat and that stimulate receptors in several areas of the brain, including the hypothalamic arcuate nucleus (ARC). Energy-rich nutrients also provide a direct signal to the ARC. These sensory inputs are integrated with circuits from other brain areas related to cognitive, social, and emotional activities, and the output alters food intake, energy expenditure, and ultimately body adiposity.

Figure 2. Satiation Signals

Satiation signals can be partitioned in terms of their relationship to the caloric content of food being eaten. Distal signals such as the taste and smell of food occur relatively early during meals and have a low and variable degree of reliability to caloric content. Intermediate signals such as CCK and GLP-1 are secreted in response to the physicochemical properties of ingested food as it interacts with receptors in the gastrointestinal lumen. Proximal signals are energy-rich nutrients themselves and/or the consequences of their local metabolism in the brain, and they arise later in time than distal or intermediate signals.

Figure 3. Modeling the Satiating Effect of an Exogenous Compound

Satiation is hypothesized to occur and the ongoing meal therefore hypothesized to end when a satiation threshold is reached. Early in a normal (control) meal (Time A), when not many calories have been consumed, mouth factors (MF) and gastric distension (GD) presumably combine with intermediate signals such as amylin (AMY), glucagon (GL), and CCK, providing an integrated satiation signal insufficient to cause the meal to end. Later during the meal (Time B), other signals such as GLP-1 (GLP) and PYY come online, increasing the total satiation signal. If an exogenous satiation factor such as CCK has been administered (test meal), the combined satiation signal (endogenous plus exogenous factors) is sufficient to reach threshold, and eating stops. Normally, however, more food is consumed (Time C), and other factors such as perhaps nutrients themselves (NUT) enter into the calculus, and the meal ends when the combined endogenous signals reach threshold.