Endocrinology and Metabolism Clinics of North America
Brain Regulation of Appetite and Satiety
Section snippets
Gut-brain connection
The gastrointestinal tract not only acts as a conduit for food but is also crucial for the digestion and absorption of nutrients. Visual, olfactory, and gustatory stimuli stimulate exocrine and endocrine secretions and gut motility even before food enters the mouth. Meal ingestion stimulates mechanoreceptors, resulting in a coordinated sequence of distension and propulsion to accommodate the mass of food and ensure digestion and nutrient absorption. The brain receives signals from the
Leptin-brain interaction
As mentioned earlier, the discovery of leptin was a major milestone in elucidation of the communication between the brain and energy stores. Leptin is expressed by adipocytes, and the concentrations of leptin in adipose tissue and plasma parallel the mass of adipose tissue and triglyceride content. Leptin is increased in obesity and falls with weight loss.35, 36 These changes are partly mediated by insulin. Leptin is transported via a saturable process across the blood-brain barrier. Moreover,
Other peripheral factors controlling feeding and metabolism
Insulin is secreted in response to meals and increases the storage of glycogen, fat, and protein. In peripheral tissues, insulin autophosphorylates the insulin receptor, leading to activation of the insulin receptor substrate (IRS) phosphatidylinositol 3-kinase (PI3K) enzyme system. Studies by Porte and colleagues,51 preceding the discovery of leptin, revealed a blood-to-brain insulin transport and binding of insulin to several regions in the brain. Most significantly, injection of insulin into
Hedonic mechanisms regulating appetite and satiety
Because eating provides energy substrates for metabolism, it is logical that eating behavior is subject to homeostatic controls described in the preceding sections; however, appetite is also driven by factors beyond physiologic needs. Food provides powerful visual, smell, and taste signals which can override satiety and stimulate feeding. We tend to overeat sweet and salty foods and consume less foods that are bitter or sour. The taste and smell of food can profoundly alter behavior; palatable
Summary
Eating behavior is critical for the acquisition of energy substrates. As discussed in this review, the gut-brain axis controls appetite and satiety via neuronal and hormonal signals. The entry of nutrients in the small intestine stimulates the release of peptides which act as negative feedback signals to reduce meal size and terminate feeding. Hormones and cytokines secreted by peripheral organs exert long-term effects on energy balance by controlling feeding and energy expenditure. Neurons
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This work was supported by National Institutes of Health grants R01-DK062348 and PO1 DK049210.