Programming of hypothalamic energy balance gene expression in rats by maternal diet during pregnancy and lactation
Résumé
Epidemiological studies show a link between low birthweight and increased obesity. In contrast, slow growth during the lactation period reduces obesity risk. This study investigates potential underlying mechanisms. Rats were established as follows: (a) controls (offspring of control dams fed a 20% protein diet), (b) recuperated animals (offspring of dams fed an isocaloric low-protein (8%) diet during pregnancy, nursed by control dams) and (c) postnatal low-protein animals (offspring of control dams nursed by low-protein dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridisation. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (p<0.05). At 21 days they were hypoleptinemic compared to controls in the fed state with generally comparable hypothalamic gene expression. Postnatal low-protein offspring had significantly lower body weight than controls at weaning and 12 weeks of age (p<0.001). At 21 days they were hypoglycemic, hypoinsulinemic and hypoleptinemic. Leptin receptor gene expression in the arcuate nucleus was increased in postnatal low-protein animals compared to controls. Consistent with the hypoleptinemia, hypothalamic gene expression for orexigenic neuropeptides, neuropeptide Y and, agouti-related peptide, was increased, and that for anorexigenic neuropeptides, proopiomelanocortin and cocaine-and amphetamine-regulated transcript was decreased. These results suggest that the early nutritional environment can affect the development of energy balance circuits and consequently obesity risk.
Origine : Fichiers produits par l'(les) auteur(s)