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Maternal prenatal undernutrition alters the response of POMC neurons to energy status variation in adult male rat offspring.

Abstract
Epidemiological studies suggest that maternal undernutrition predisposes the offspring to development of energy balance metabolic pathologies in adulthood. Using a model of a prenatal maternal 70% food-restricted diet (FR30) in rats, we evaluated peripheral parameters involved in nutritional regulation, as well as the hypothalamic appetite-regulatory system, in nonfasted and 48-h-fasted adult offspring. Despite comparable glycemia in both groups, mild glucose intolerance, with a defect in glucose-induced insulin secretion, was observed in FR30 animals. They also exhibited hyperleptinemia, despite similar visible fat deposits. Using semiquantitative RT-PCR, we observed no basal difference of hypothalamic proopiomelanocortin (POMC) and neuropeptide Y (NPY) gene expression, but a decrease of the OB-Rb and an increase of insulin receptor mRNA levels, in FR30 animals. These animals also exhibited basal hypercorticosteronemia and a blunted increase of corticosterone in fasted compared with control animals. After fasting, FR30 animals showed no marked reduction of POMC mRNA levels or intensity of beta-endorphin-immunoreactive fiber projections. By contrast, NPY gene expression and immunoreactive fiber intensity increased. FR30 rats also displayed subtle alterations of food intake: body weight-related food intake was higher and light-dark phase rhythm and refeeding time course were modified after fasting. At rest, in the morning, hyperinsulinemia and a striking increase in the number of c-Fos-containing cells in the arcuate nucleus were observed. About 30% of the c-Fos-expressing cells were POMC neurons. Our data suggest that maternal undernutrition differently programs the long-term appetite-regulatory system of offspring, especially the response of POMC neurons to energy status and food intake rhythm.
AuthorsChristophe Breton, Marie-Amélie Lukaszewski, Pierre-Yves Risold, Mihaela Enache, Johann Guillemot, Guillaume Rivière, Fabien Delahaye, Jean Lesage, Isabelle Dutriez-Casteloot, Christine Laborie, Didier Vieau
JournalAmerican journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 296 Issue 3 Pg. E462-72 (Mar 2009) ISSN: 0193-1849 [Print] United States
PMID19088253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hormones
  • Insulin
  • Neuropeptide Y
  • Receptors, Leptin
  • beta-Endorphin
  • Pro-Opiomelanocortin
  • Receptor, Insulin
Topics
  • Animals
  • Appetite (physiology)
  • Arcuate Nucleus of Hypothalamus (cytology, physiology)
  • Body Composition (physiology)
  • Body Weight (physiology)
  • Eating (physiology)
  • Energy Metabolism (physiology)
  • Feeding Behavior (physiology)
  • Female
  • Fetal Nutrition Disorders (metabolism)
  • Genes, fos (physiology)
  • Glucose Tolerance Test
  • Hormones (blood)
  • Insulin (blood)
  • Litter Size
  • Male
  • Neurons (metabolism)
  • Neuropeptide Y (genetics, metabolism)
  • Pregnancy
  • Prenatal Exposure Delayed Effects (metabolism)
  • Pro-Opiomelanocortin (genetics, metabolism)
  • Rats
  • Rats, Wistar
  • Receptor, Insulin (genetics)
  • Receptors, Leptin (genetics)
  • beta-Endorphin (metabolism)

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