Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 364

Hormones that influence food intake include leptin, ghrelin, and the orexins. Additionally, the central feeding system is dependent on the stimulatory effect of neurotransmitters, including the opioids, noradrenaline, neuropeptide Y (NPY), and galanin. A recent systematic review and meta‐analysis suggest that there are increased concentrations of inhibitory hormones including insulin, leptin, CCK, and PYY circulating in older adults.³³

The short‐term peripheral satiety system is largely driven by gastrointestinal mechanisms. In the longer term, factors such as leptin and cytokines become more important. Gastrointestinal sensory and motor functions are essential in the regulation of satiation. Sensory signals induced by the distension by food contribute to initial sensations of fullness during a meal. These sensations are mediated via vagal mechanisms from mechanoreceptors situated within the stomach wall. In young adult humans, gastric distension using a barostat reduces food intake by up to 30%. Distension of the distal stomach (antrum) is related to increased sensations of fullness and is likely to be more important than distension of the proximal stomach (fundus). After eating, the stomach relaxes by a process of receptive relaxation, resulting in decreased intragastric pressure and increased gastric volume. This relaxation is particularly marked in the proximal stomach and results in a proximal fundic reservoir where food is retained. Not long before it is emptied into the small intestine, food is propelled distally from the fundus into the antrum. The extent of antral filling and distension relates more closely to feelings of fullness and satiety than does proximal gastric distension.³⁰ Studies in animals and humans have demonstrated a relationship between postprandial satiety and the rate of gastric emptying. Slowing of gastric emptying may reduce appetite and food intake by increasing and prolonging antral distension and by prolonging the effect of small intestinal satiety signals. People with gastroparesis often exhibit symptoms of early satiety, loss of appetite, nausea, and vomiting, and studies in both animals and humans have shown that there is a relationship between postprandial satiation and the rate of gastric emptying.

Once food has entered the small intestine, chemoreceptors relay signals to the hypothalamus, resulting in the cessation of food intake. These signals are mediated by the release of gastrointestinal peptide hormones including CCK, peptide YY (PYY), and glucagon‐like peptide‐1 (GLP‐1). A number of gastrointestinal and pancreatic hormones, including CCK, GLP‐1 and amylin, have feedback effects on the stomach to slow gastric emptying, an effect associated with increased fullness and reduced food intake, by increasing and prolonging gastric distension and prolonging the effect of small intestinal satiety signals. Nutrient absorption and feedback signals from peripheral fat cells via leptin and, possibly, TNF‐α contribute to satiation.

Figure 13.1 illustrates the interplay of these mechanisms involved in appetite regulation. While evidence may be limited, Figure 13.2 summarizes which hormones are thought to be stimulatory and inhibitory.