Moderate caloric restriction during gestation affects offspring hypothalamic structure and function, impairing its response to fed/fasting conditions

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

Estocolmo

Congreso; 11th International Congress of Obesity; 2010

ABSTRACT Aim: We aimed to characterize the developmental programming effects of moderate caloric restriction during early pregnancy on factors involved in hypothalamic control of energy balance. Methods: Twenty-five-days-old offspring Wistar rats from 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied under fed and 12-h fasting conditions. Morphometric studies on arcuate nucleus (ARC) and determinations of circulating parameters and hypothalamic levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), long-form leptin receptor (ObRb), insulin receptor (InsR) and suppressor of cytokine signalling-3 (SOCS-3) mRNA were performed. Results: CR animals did not show different body weight with respect to their controls, but presented higher food intake. They exhibited lower NPY- and α-melanocyte-stimulating hormone-neurons (decreases of 18 and 13% in males, and 10 and 18% in females respectively) and lower total cells (decrease of 3% in males and 18% infemales) in ARC. Under fed conditions, CR animals presented lower circulating leptin and ghrelin levels; furthermore, hypothalamic POMC, NPY (only in females), ObRb and InsR mRNA levels were reduced, and those of SOCS-3 were increased. Unlike control animals, under fasting conditions, ObRb, InsR and POMC mRNA levels did not decrease in CR females, and NPY mRNA decreased instead of increase in CR males. Conclusions: Moderate caloric restriction during gestation affects offspring hypothalamic structure and function, impairing its response to fed/fasting conditions, which suggests a predisposition to insulin and leptin resistance.