Abstract

To maintain nutrient homeostasis the central nervous system integrates signals that promote appetite or satiety. In mammals a protein preload decreases food intake more profoundly than a carbohydrate‐ or a fat preload. We hypothesized that this effect is based on the sensing of specific amino acids (AA) as a signal to control food intake. Orally applied Arg, Lys and Glu decreased subsequent food intake by 50%, 47%, and 35%, respectively, whereas all other proteogenic AA had no effect relative to water control in rats. Decreased food intake correlated with gastric distension as isovolumetric doses of Arg, Lys and Glu increased stomach wet weight by 220%, 260%, and 144%. These behavioral and autonomic responses are controlled by neurons in specific brain areas. Increased neuronal activity, tested by counting c‐Fos positive cells, was detected in the blood‐sensing area postrema and the nucleus of the solitary tract. To test whether circulating AA directly signal to the brain, we administered Arg, Lys and Glu intravenously (2mmol/kg). All three AA induced an anorectic response that was similar to the one induced after oral application. Surgical lesion of the area postrema abolished the anorectic responses of Arg and Glu but not of Lys. We presume that Arg and Glu act in the area postrema to cause the anorectic response, while Lys might stimulate hepatic vagal afferents projecting to the nucleus of the solitary tract.

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