The Physiology of Meals
Investigations of how the brain uses sensory information to control eating, or bottom-up analyses, indicate that a 2-tiered neural network mediates eating.[14,15] The core tier, located in the hindbrain, comprises afferent neurons that relay positive and negative feedback from peripheral physiologic events, interneuronal networks that process this information, and efferent neurons that produce the motor acts of ingestion. In decerebrate rats, the core tier is sufficient to determine whether to ingest or reject food and how much food to consume.
Overlying the core tier is a forebrain tier, which receives conditioned and unconditioned interoceptive and exteroceptive stimuli and mediates food search, food choice, meal timing, and the elaboration of the basic behavior mechanisms of eating into subjective experiences. Because the neural machinery controlling the motor acts of ingestion are part of the core tier, forebrain mechanisms ultimately affect eating through efferents that converge on the hindbrain in a way analogous to the convergence of the brain mechanisms of movement on local neural networks in the spinal cord.
Controls of Meal Size
At present, the best understood physiologic mechanisms mediating meal-taking behaviors are the feedback signals arising from the action of ingested food on preabsorptive receptors during the meal -- that is, the direct controls of meal size. The critical receptors for the direct controls of meal size are localized in the oropharynx, stomach, and upper small intestine (Table I). These food stimuli initiate afferent signals, encoded mainly as vagal neural activity and as concentrations of peptides in the plasma. The basic behavioral consequences of these feedback signals are mediated by the core tier of hindbrain neural networks. The preabsorptive locations of their receptors and their rapid, intrameal actions make these signals uniquely accessible for study.
Indirect controls of meal size comprise a large, heterogenous category, including physiologic functions such as metabolism (influence of altered body adiposity or energy expenditure) and immune response (sepsis or cancer). Other indirect controls are conditioned and range from flavor preferences, to social and cultural influences, to complex, individuated cognitive and emotional consequences of life history. Abnormalities in such cognitive and emotional indirect controls are usually assumed to cause disordered human eating. Indeed, the exaggerated eating response of patients with bulimia nervosa, when they were instructed to binge in the laboratory, may be an example of such an abnormal cognitive control. For example, in a laboratory setting, Kissileff and colleagues asked patients with bulimia nervosa or control subjects to consume a yogurt shake after being instructed to binge, and observed that the patients ate much more (ie, 1597 vs 1004g). However, the neural mechanisms of indirect controls of meal size are not wholly independent from the mechanisms of more basic physiologic controls. Indirect controls typically produce tonic effects, acting for longer periods than the duration of individual meals. As part of the forebrain tier of networks, indirect controls influence meal size by modulating the potencies of direct controls (Fig. 4). Because of the lack of variation in plasma estradiol levels before or after individual meals, estradiol appears to exert indirect controls.
Figure 4. Schematic of feedbacks that mediate direct and indirect controls of meal size. (1) Direct controls of meal size are initiated by feedback arising from action of food stimuli on preabsorptive receptors during the meal. (2) Information encoded as neural and endocrine signals act as positive and negative feedback to hindbrain neural networks that (3) control motor acts of eating and (4) provide input to forebrain mechanisms that mediate subjective phenomena associated with eating. (5) Indirect controls arise from wide variety of stimuli, including estradiol, providing feedback to forebrain. (6) Forebrain neural networks converge on hindbrain networks to influence eating.
The physiology of eating has been approached from the top by beginning with the analysis in the brain. This work has identified a number of amines and peptides whose central administration affects meal size in animals and humans, presumably by affecting the interneuronal networks that mediate direct and indirect controls of meal size. It is now possible to manipulate and measure brain neurochemicals at the sites of their biological action during meals in animals, but little work of this type has addressed sex differences in eating.
Less powerful methods, such as measurements of neurotransmitter or metabolite concentrations in the cerebrospinal fluid, are possible in humans. Unfortunately, these methods generally cannot be done in the context of eating. Nevertheless, such methods have shown that the function of several neurotransmitter systems is altered in patients with eating disorders.[18,19,20] The physiologic causes of these changes and whether they contribute to or result from the eating disorders remain to be determined.
The relationship of these neurotransmitter systems to the indirect control of meal size exerted by estradiol is unknown. This connection is difficult to study because individual neurotransmitters are involved in numerous functional neural networks, and the techniques now available for analysis in humans fail to relate observed effects to particular networks. For example, all neurotransmitters reported to change in anorexia nervosa are involved in the control of gonadotropin release, as well as the control of eating in animals.
Medscape General Medicine. 1998;1(3) © 1998
Cite this: The Effect of Estrogen on Appetite - Medscape - Nov 19, 1998.