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

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

DIABETES OBESITY & METABOLISM

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 12 p. 403 - 413

1462-8902

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: 25d-old offspring Wistar rats from 20% caloric restricted dams (from 1-12d of pregnancy) (CR) and from control dams were studied under fed and 12h-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 respect their controls, but presented higher food intake. They exhibited lower neuropeptide Y- 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% in females) in ARC. Under fed conditions, CR animals presented lower circulating leptin and ghrelin levels (decreases of 37% and 43% in males, and 15% and 34% in females respectively); furthermore, hypothalamic POMC, NPY (only in females), ObRb and InsR mRNA levels were reduced (39%, 16% and 26% in males, and 112%, 33%, 61% and 56% in females), and those of SOCS-3 were increased (86% in males and 74% in females). 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.