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.
OBJECTIVE
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 neuropeptide Y- and alpha-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.
García
A P
AP
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of Balearic Islands and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
Palou
M
M
Priego
T
T
Sánchez
J
J
Palou
A
A
Picó
C
C
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000378:metabolism; D031204:Caloric Restriction; D004435:Eating / Q000235:genetics / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D020738:Leptin; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014886:Weaning; D000521:alpha-MSH / Q000378:metabolism*
D020738:Leptin; D009478:Neuropeptide Y; D011498:Protein Precursors; D000521:alpha-MSH