Moderate caloric restriction during gestation results in lower arcuate nucleus NPY- and αMSH-neurons and impairs hypothalamic response to fed/fasting conditions in weaned rats

A. P. GARCÍA; M. PALOU; T. PRIEGO; J. SÁNCHEZ; C. PICÓ

Montecatini

Conferencia; The NuGOweek 2009, The sixth European Nutrigenomics Conference; 2009

ABSTRACT Maternal prenatal undernutrition has long-term consequences on offspring energy regulatory systems, increasing the propensity to obesity. The aim of this study was to characterise the early effects of moderate maternal caloric restriction during gestation on main central structures and factors involved in the control of food intake and energy homeostasis in offspring rats. The study was performed in 25-day-old male and female offspring of dams that underwent a 20% caloric restriction during the first 12 days of pregnancy (CR group) or from ad libitum fed mothers (C group). Circulating levels of glucose, insulin, leptin and ghrelin and hypothalamic mRNA levels of neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), long-form leptin receptor (ObRb), insulin receptor (InsR), suppressor of cytokine signalling-3 (SOCS-3) and ghrelin receptor (GHSR) were measured under fed and 12 h fasting conditions. Morphometric studies on arcuate (ARC) nucleus of hypothalamus (number of cells and number of NPY and α-melanocyte-stimulating hormone immunoreactive neurons, NPY+ and αMSH+ respectively) were performed in a separate group of animals under fed conditions. At the age of 25 days, no differences were found in body weight and adiposity between both groups of animals, although CR animals showed higher cumulative caloric intake (measured from weaning on day 21 until day 25 of life) and lower circulating leptin and ghrelin levels than their controls. Maternal caloric restriction was able to produce significant structural changes on offspring hypothalamus, resulting in a reduced number of cells and in the number of NPY+ and αMSH+ in ARC nucleus, in both males and females. Hypothalamic mRNA expression levels of AgRP, POMC and CART were significantly reduced in male and female CR groups, and those of NPY were reduced only in females. mRNA levels of ObRb and InsR were significantly reduced in CR males and females, and those of SOCS-3 resulted significantly increased. The offspring of caloric restricted mothers also showed an impaired response to fed/fasting conditions. In particular, C female animals exhibited a decrease in ObRb, InsR and POMC mRNA levels under fasting conditions, whereas this response was not seen in CR female animals. C males showed a significant increased in NPY mRNA levels under fasting conditions, whereas mRNA levels of this neuropeptide were significantly reduced in fasted CR males. In conclusion, moderate maternal undernutrition during the first part of pregnancy leads in profound effects in the offspring hypothalamic structure and alters gene expression pattern of factors involved in the control of food intake and energy expenditure. In addition, these animals show lower capacity to adequately respond to fed/fasting conditions at the central level, which can be indicative of a predisposition to central insulin and leptin resistance.