Programming of hypothalamic neuropeptide gene expression in rats by maternal dietary protein content during pregnancy and lactation
- 15 June 2009
- journal article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 117 (2), 85-93
- https://doi.org/10.1042/cs20080393
Abstract
Epidemiological studies show a link between low birthweight and increased obesity. In contrast, slow growth during the lactation period reduces obesity risk. The present study investigates the potential underlying mechanisms of these observations. Rats were established as follows: (i) control animals [offspring of control dams fed a 20% (w/v) protein diet], (ii) recuperated animals [offspring of dams fed an isocaloric low-protein (8%, w/v) diet during pregnancy and nursed by control dams], and (iii) postnatal low protein animals (offspring of control dams nursed by low-protein-fed dams). Serum and brains were collected from fed and fasted animals at weaning. Expression of hypothalamic energy balance genes was assessed using in situ hybridization. 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 hypoleptinaemic compared with controls in the fed state, with generally comparable hypothalamic gene expression. Postnatal low protein offspring had significantly lower body weights than controls at weaning and 12 weeks of age (P<0.001). At 21 days, they were hypoglycaemic, hypoinsulinaemic and hypoleptinaemic. Leptin receptor gene expression in the arcuate nucleus was increased in postnatal low protein animals compared with controls. Consistent with hypoleptinaemia, hypothalamic gene expression for the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (Agouti-related peptide) was increased, and that for the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (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.Keywords
This publication has 34 references indexed in Scilit:
- Breast-feeding and childhood obesity—a systematic reviewInternational Journal of Obesity, 2004
- Early programming of weight gain in mice prevents the induction of obesity by a highly palatable dietClinical Science, 2004
- Catch-up growth and obesity in male miceNature, 2004
- ObesityClinical Medicine, 2003
- Prevalence and Trends in Obesity Among US Adults, 1999-2000JAMA, 2002
- Childhood Obesity and a Diabetes EpidemicNew England Journal of Medicine, 2002
- Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutritionAmerican Journal of Physiology-Endocrinology and Metabolism, 2000
- Fetal and infant growth and impaired glucose tolerance at age 64.BMJ, 1991
- WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASEThe Lancet, 1989
- Obesity in Young Men after Famine Exposure in Utero and Early InfancyNew England Journal of Medicine, 1976