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Fat Preference: A Novel Model of Eating Behavior in Rats
Published on: June 27, 2014
Moderate caloric restriction during gestation results in lower arcuate nucleus NPY- and alphaMSH-neurons and impairs
A P García1, M Palou, T Priego
1Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of Balearic Islands and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain.
Insights
Moderate caloric restriction in pregnant rats alters offspring
Area of Science:
- Developmental programming
- Neuroendocrinology
- Energy balance regulation
Background:
- Maternal nutrition during pregnancy influences offspring's long-term health.
- Hypothalamic pathways control energy homeostasis.
- Caloric restriction is a known modulator of metabolic processes.
Purpose of the Study:
- To investigate the effects of moderate maternal caloric restriction during gestation on hypothalamic factors controlling energy balance in offspring.
- To characterize developmental programming induced by gestational nutrient scarcity.
Main Methods:
- Wistar rats were subjected to 20% caloric restriction during early pregnancy.
- Offspring were studied at 25 days old under fed and fasted states.
- Arcuate nucleus morphometry and quantification of hypothalamic neuropeptide Y (NPY), proopiomelanocortin (POMC), leptin receptor (ObRb), insulin receptor (InsR), and suppressor of cytokine signalling-3 (SOCS-3) mRNA were performed.
Main Results:
- Caloric-restricted offspring exhibited increased food intake but no difference in body weight.
- Reduced neuronal populations (NPY, POMC) and lower mRNA levels of POMC, NPY, ObRb, and InsR were observed in the arcuate nucleus.
- Circulating leptin and ghrelin levels were decreased in caloric-restricted offspring.
- Suppressor of cytokine signalling-3 (SOCS-3) mRNA levels were elevated.
- Offspring from restricted dams showed altered responses to fasting, with blunted changes in ObRb, InsR, and POMC mRNA in females and paradoxical NPY mRNA changes in males.
Conclusions:
- Moderate gestational caloric restriction impacts offspring's hypothalamic structure and function.
- This programming impairs the hypothalamic response to feeding and fasting states.
- The findings suggest a predisposition to insulin and leptin resistance in offspring exposed to maternal caloric restriction.
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 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.

