Zusammenfassung
Die Nahrungsaufnahme wird kontrolliert durch das zentrale Nervensystem, das für den Beginn des Essens verantwortlich ist („feeding drive”) und ein peripheres Sättigungssystem, das durch die Gegenwart von Nahrung im Gastrointestinaltrakt aktiviert wird. Die zentrale Appetitregulation wird über verschiedene Neurotransmitter mediiert, nämlich endogene Opioide, Neuropeptid Y, Noradrenalin und Serotonin. Beim Menschen ist besonders die Wirkung endogener Opioide belegt, da ein Opiatantagonist die Nahrungsaufnahme hemmt. Die gastrointestinalen Sättigungsfaktoren sind die gastrale Distension, dabei besonders die des Antrums, die Magenentleerung und die Aktivierung intestinaler Sättigungsmechanismen. Dabei kommt besonders dem Cholezystokinin eine wesentliche Rolle zu. Die physiologische Anorexie des alten Menschen bezeichnet eine Abnahme des Appetits und eine Zunahme der Sättigung als immanente Vorgänge im Alter. Diese Anorexie prädisponiert zu Mangelernährung, insbesondere dann, wenn somatische oder psychische Erkrankungen hinzukommen. Im Alter ist die Diskriminierungsfähigkeit des Gastrointestinaltrakts gegenüber externen Stimuli beeinträchtigt. Darüber hinaus scheint die verzögerte Clearance des Sättigungshormons CCK aus dem Plasma beim alten Menschen ein anorexigener Faktor zu sein. Etablierte pharmakologische Ansätze zur Reduktion der Nahrungsaufnahme sind der Serotonin- und Noradrenalinwiederaufnahmehemmer Sibutramin und der Lipaseinhibitor Orlistat. Neue experimentelle Ansätze, zu denen es beim Menschen noch keine Daten gibt, zielen darauf hin, Neuropeptid-Y-exprimierende Neurone im Hypothalamus zu hemmen bzw. Neurone, die Proopiomelanocortin exprimieren, zu stimulieren. Auch zwei periphere Enzymsysteme sind potenzielle Ziele zur Therapie der Adipositas, nämlich die Azetyl-CoA-Carboxylasen und die Fettsäuresynthase.
Abstract
Food intake is controlled by the central nervous system which initiates eating (feeding drive) and by peripheral satiety signals which are activated by the presence of food in the gastrointestinal tract. Central regulation of appetite is mediated via several transmitters, especially endogenous opioids, neuropeptide Y, noradrenaline and serotonin. In man the effect of endogenous opioids was demonstrated by studies showing an opioid antagonist to inhibit food intake. The predominant factors mediating satiation are gastric distention, especially antral distention, gastric emptying and the activation of intestinal satiation signals. The predominant hormonal mediator of satiation is cholecystokinin. Anorexia of aging refers to an inherent reduction of appetite and increase in satiation during the process of aging. This anorexia renders the elderly susceptible to malnutrition, especially if somatic or psychiatric diseases occur. During the course of aging the gastrointestinal tract becomes less sensitive to discriminate differential external stimuli. Prolonged plasma clearance of the satiety hormone CCK apears to be an anoroexigenic factor. Established pharmacological approaches to reduce food intake are sibutramine which inhibits uptake of serotonin and noradrenalin and orlistat which inhibits pancreatic lipase. Novel approaches which remain to be tested in man aim at stimulating hypothalamic neurons which express neuropeptide Y or inhibiting neurons expressing proopiomelanocortin. Moreover two peripheral enzyme systems are potential targets for therapy of obesity, i.e. acetyl-CoA-carboxylases and fatty acid synthase.
Schlüsselwörter
Anorexie im Alter - Cholezystokinin - Glukagon-like peptide-1 - Orlistat - Pharmakotherapie der Adipositas - Sibutramin
Key words
Anorexia of aging - cholecystokinin - glucagon-like peptide-1 - orlistat - pharmacotherapy of obesity - sibutramine
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Prof. Dr. M. Katschinski
Ev. Diakonie-Krankenhaus · Medizinische Klinik
Gröpelinger Heerstraße 406 - 408
28239 Bremen
