Perinatal protein restriction reduces the inhibitory action of serotonin on food intake.
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.
Lopes de Souza
Sandra
S
INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Nantes, France.
Orozco-Solis
Ricardo
R
Grit
Isabelle
I
Manhães de Castro
Raul
R
Bolaños-Jiménez
Francisco
F
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D018753:Diet, Protein-Restricted / Q000379:methods; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006963:Hyperphagia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D012701:Serotonin