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Perinatal protein restriction reduces the inhibitory action of serotonin on food intake.

Abstract : Early malnutrition has been associated with a high risk of developing obesity, diabetes and cardiovascular diseases in adulthood. In animals, poor perinatal nutrition produces hyperphagia and persistent increased levels of serotonin (5-HT) in the brain. Inasmuch as 5-HT is directly related to the negative regulation of food intake, here we have investigated whether the anorexic effects of 5-HT are altered by protein malnutrition. Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 35 days their feeding behaviour was evaluated after the administration of DL-fenfluramine (DL-FEN), an anorexic compound that blocks the reuptake of 5-HT and stimulates its release. Male offspring born to protein-restricted dams exhibited significantly decreased body weight and hyperphagia compared with controls. DL-FEN dose-dependently reduced the 1 h chow intake at the onset of the dark cycle in both control and undernourished rats. However, the hypophagic effects of DL-FEN were significantly attenuated in animals submitted perinatally to protein restriction. The stimulatory action of DL-FEN on c-fos immunoreactivity within the paraventricular nucleus of the hypothalamus was also decreased in low-protein-fed rats. Further pharmacological analysis with selective 5-HT(1B) and 5-HT(2C) receptor agonist showed that the reduced anorexic effects of 5-HT in malnourished animals were coupled to a desensitization of 5-HT(1B) receptors. These observations indicate that the hyperphagia associated with metabolic programming is at least partially related to a reduced regulatory function of 5-HT on food intake.
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Submitted on : Saturday, May 30, 2020 - 12:50:14 PM
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Sandra Lopes de Souza, David Ricardo Orozco-Solis, Isabelle Grit, Raul Manhães de Castro, Francisco Bolaños-Jiménez. Perinatal protein restriction reduces the inhibitory action of serotonin on food intake.. European Journal of Neuroscience, Wiley, 2008, 27 (6), pp.1400-1408. ⟨10.1111/j.1460-9568.2008.06105.x⟩. ⟨hal-02658768⟩

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