Detrimental effects of moderate caloric restriction during gestation on later control of energy homeostasis may be related with altered hipothalamic development

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

Palma de Mallorca

Simposio; 1st Bioclaims Symposium; 2010

ABSTRACT Nutritional disturbances at a critical period of early life could determine the future metabolic health and the propensity to adverse health outcomes, including obesity and its related pathologies. Here, we aimed to study the lasting effects of a moderate caloric restriction in pregnant rats on energy homeostasis of their offspring and characterize its developmental programming effects on factors involved in hypothalamic control of energy balance. Dams were fed with either ad libitum standard diet or a 20% caloric restricted diet from 1-12 days of pregnancy. After weaning, the offspring (controls and caloric restricted (CR) animals) were fed with a normal-fat diet until the age of 4 months, and then with a high-fat diet until the age of 5 months. Body weight, fat body content and cumulative food intake were measured. Morphometric analysis were performed on arcuate nucleus (ARC), 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 levels and circulating parameters were measured under fed and 12-h fasting conditions in 25 day-old animals. Accumulated caloric intake from weaning to the age of 5 months was higher in CR animals compared with their controls, and this resulted in higher body weight in adulthood in males, but not in females. On day 25 of life, CR animals did not show changes in body weight but presented higher food intake. They exhibited lower NPY- and α-melanocyte-stimulating hormone-neurons and lower total cells 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 12-h fasting conditions, ObRb, InsR and POMC mRNA levels did not decrease in CR females, and NPY mRNA decreased instead of increase in CR males. In summary, moderate caloric restriction during gestation produces important effects in the offspring hypothalamic development of structures and factors involved in the control of food intake and energy expenditure that may be responsible for their higher food intake, and therefore predispose them to become obese in adulthood, particularly in male animals and under an obesogenic environment.