Moderate caloric restriction during gestation in rats impairs insulin and leptin sensitivity in the offspring

M. PALOU; J. KONIECZNA; JM TORRENS; J. SÁNCHEZ; T. PRIEGO; AP GARCÍA; ML FERNANDES; A. PALOU; PICÓ C

Madrid

Conferencia; 11th European Nutrition Conference (FENS); 2011

Federation of European Nutrition Societies

ABSTRACT We have previously described that 20% caloric restriction in rats during the first half of gestation results in higher food intake in their offspring and this concludes in higher body weight in males but not in females. Here, we aimed to assess the mechanisms responsible for hyperphagia and metabolic alterations caused by maternal caloric restriction during gestation in offspring. Male and female offspring of 20% caloric restricted rats (from 1 to 12 days of pregnancy) (CR) and from controls were studied. These animals were, after weaning, fed a normal-fat (NF) diet until the age of 4 months, and then moved to a high-fat (HF) diet until the age of 6 months. Blood parameters and expression of selected genes in hypothalamus, retroperitoneal white adipose tissue (rWAT) and liver were analyzed at 25-days and 6-months of age. Plasma leptin was also measured during suckling. CR animals ate more calories than controls, but only males gained more weight. A peak in plasma leptin was found in control pups at the age of 9 days, but was absent in CR animals. 25-day-old CR animals showed lower mRNA levels of InsR in hypothalamus, rWAT and liver, and of ObRb in hypothalamus. At the age of 6 months, HOMA-IR index was higher in CR rats than controls, and CR males also displayed hyperleptinemia. Adult CR animals also showed lower ObRb mRNA levels in the hypothalamus (only females, but both showed altered NPY/POMC mRNA ratio), rWAT, and liver (males). These results suggest CR rats are programmed for insulin and central leptin resistance, which may explain the dysregulation of appetite and other metabolic alterations, leading to a context favorable to obesity and diabetes development. These early programming effects could be associated with the absence of leptin surge during lactation.