Elsevier

Physiology & Behavior

Volume 81, Issue 2, April 2004, Pages 249-273
Physiology & Behavior

Gastrointestinal mechanisms of satiation for food

https://doi.org/10.1016/j.physbeh.2004.02.012Get rights and content

Abstract

Satiation for food comprises the physiological processes that result in the termination of eating. Satiation is evoked by physical and chemical qualities of ingested food, which trigger afferent signals to the brain from multiple sites in the GI tract, including the stomach, the proximal small intestine, the distal small intestine and the colon. The physiological nature of each signal's contribution to satiation and overall control of food intake is likely to vary, depending on the level of the GI tract from which the signal arises. This article is a critical, though non-exhaustive, review of our current understanding of the mechanisms and adaptive value of satiation signals from the stomach and intestine.

Introduction

The conviction that the gastrointestinal tract controls appetite for food is rooted in antiquity. It probably predates literary and artistic references to hunger and satiation that appear early in written historical records and persists in popular culture today. The potent and persistent association between food intake and the gastrointestinal tract derives from the fact that the gastrointestinal tract is highly innervated by sensory neurons and refers robust sensations, which are directly related to physical and chemical stimulation by ingested food.

Some of the earliest experimental attempts to link the gastrointestinal tract with control of food intake were undertaken by W.B. Cannon and his student Washburn (1912). Cannon and Washburn recorded and correlated the strength of gastric contractions with conscious sensations that Cannon termed “hunger pangs”. While Cannon's efforts focused on the role of the gastrointestinal tract in the sensation of hunger, the desire to seek and eat food, he was acutely aware of the process of satiation. In his monograph, “The wisdom of the body” [229], he concluded:

Cooperating with hunger and thirst in a way not yet clearly defined is the sensation of having had enough. Protection of the organism against being overstocked with food and water is thus obtained. The feeling of satiation is little understood, but it is important and deserves further attention.

Couched as it is in his discourse on the role of the gastrointestinal tract in the sensation of hunger, three messages can be drawn from Cannon's statement. First, satiation derives, at least in part, from gastrointestinal signals. Second, satiation serves a protective function. And, third the mechanisms by which satiation occurs are incompletely understood. The situation has changed markedly in the last two decades, during which time satiation has received quite a lot of attention. Much of this attention has been focused on the role of the gastrointestinal tract in providing signals that control the process of satiation, a process which manifests itself in meal termination.

In his use of the term “feeling of satiation” Cannon seems to imply that satiation involves conscious awareness of feedback signals, or at least an affective response to them. Indeed, studies of human subjects commonly assess the sensation of fullness using an analogue rating scale. However, there is no direct evidence that a conscious awareness of gastrointestinal feedback signals is necessary for satiation. In fact, gastrointestinal signals can control meal size in rats even in the absence of forebrain structures, which seem essential for sensory-perceptual function and affect. For example, rats that have been decerebrated at the collicular level exhibit satiation [90], [92], and even display taste reactivity patterns that are associated with positive and negative gustatory properties of foods [91]. Nevertheless, few would argue that other components of conscious sensation or affect are preserved in the decerebrate preparation. Thus, gastrointestinal feedback to the caudal brainstem is sufficient for satiation. However, the participation of forebrain structures associated with feelings and conscious perception in satiation remains to be systematically investigated.

The most compelling experimental evidence for GI involvement in satiation is that the removal of ingesta from the gastrointestinal tract during the ingestion of a meal increases food intake. In the mid- to late 1800s, human case reports indicated that people with gastric or intestinal fistulas remained hungry when most of the food they ate drained from the upper GI tract [30]. In 1895, Shumova-Simonovskia and Pavlov reported that dogs with experimental esophageal fistulas ate continuously, suggesting that stimuli for satiation were absent or attenuated [159]. More recent experiments, using chronically implanted esophageal [146] or gastric [81] cannulas, have enabled better control of the nutritional condition of experimental subjects, while providing temporal and kinetic information that convincingly demonstrates inhibition of food intake by the gastrointestinal tract. For example, animals in good nutritional condition, with chronically implanted gastric cannulas, eat continuously on test days when food is allowed to drain from the cannula. However, the same animals terminate ingestion rapidly when the cannula is closed, allowing ingesta to fill the stomach and empty to the small intestine [54], suggesting that the stomach and/or intestine provide signals that contribute to satiation for food.

In this review, I intend to focus first on the locations from which the gastrointestinal sensory signals that contribute to satiation arise and on the physical/chemical nature of these signals. I also will discuss the potential mechanisms by which the signals are communicated to the central nervous system. Finally, I will conclude with recent results suggesting that sensitivity to intestinal signals that lead to satiation adapt in response to dietary conditions, and how this adaptation may be consistent with a protective function of satiation, vis-a-vi the gastrointestinal tract.

The review only considers processes originating from the stomach and the small intestine and does not deal with potentially important signals that might arise pregastrically or from the large intestine or liver. Finally, I have attempted a fairly broad coverage, and no single area is exhaustively covered. With regard to the mechanisms and humoral mediators of satiation, ignorance far exceeds knowledge. In this area, I have taken the liberty of speculating on what seem to me promising leads.

Section snippets

Gastric satiation signals

A variety of experimental results indicate that the stomach provides some of the inhibitory signals that participate in satiation. The stomach receives extensive sensory innervation from the vagus nerve [168] and spinal afferents via the splanchnic innervation [152]. In the rat topographical examination of anterogradely labeled vagal afferent, endings suggest that the stomach is the most heavily innervated visceral organ [232] and a prime candidate for GI monitoring of ingestion.

Satiation signals from the intestine

Most enzymatic digestion and absorption of macronutrients occurs in the proximal small intestine. Consequently, the small intestine comprises the final opportunity for monitoring ingesta prior to absorption and assimilation. The intestinal mucosa and submucosa are extensively innervated by vagal afferents [13], which communicate with higher order neurons in the hindbrain and forebrain. In addition, the small intestine secretes a cadre of peptides that may serve as humoral afferents, informing

Summary and synthesis

Current experimental results on control of food intake by signals from the gastrointestinal tract present an intriguing but complex picture. Studies on the effects of dietary adaptation to fat, as well as some other findings, suggest that satiation signals from the GI tract function to limit ingestion in the interest of efficient digestion. Afferent signals arise from the entire length of the GI tract, including the stomach, the proximal small intestine, the distal small intestine and the

Acknowledgements

This paper was supported in part by the National Institute of Health grant NS20561.

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