Abstract
AimWe aimed to characterize the lasting effect of moderate caloric restriction during early pregnancy on offspring energy homeostasis, by focusing on the effects on food intake and body weight as well as on the insulin and leptin systems.MethodsMale and female offspring of 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied. These animals were fed after weaning with a normal-fat (NF) diet until the age of 4 months, and then moved to a high-fat (HF) diet. Blood parameters were measured under fed and 14-h fasting conditions at different ages (2, 4 and 5 months). Food preferences were also assessed in adult animals.ResultsAccumulated 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. Both male and female CR animals already showed higher insulin levels at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of 4 months, compared with their controls. CR male animals, but not females, displayed higher preference for fat-rich food than their controls in adulthood and higher circulating leptin levels when they were under HF diet.ConclusionIt is suggested that hyperinsulinemia may play a role in the etiology of hyperphagia in the offspring of caloric restricted animals during gestation, with different outcomes on body weight depending on the gender, which could be associated with different programming effects on later leptin resistance.
Highlights
There is a growing body of evidence showing that the nutritional environment during early life may have later effects on the propensity to suffer from obesity and its related metabolic pathologies [1,2]
Most of the studies in this sense have addressed the effects of severe caloric restriction, which is known to result in marked fetal growth retardation, whereas, to the best of our knowledge, the lasting effects of moderate, less severe caloric restriction during gestation on energy homeostasis in both male and female offspring have not been directly studied
We have previously described that a moderate caloric restriction of 20% during the first 12 days of pregnancy affects the normal development of hypothalamic structure and function, factors involved in insulin and leptin central action, and impairs hypothalamic response to fed/fasting conditions in weaned rats, suggesting a predisposition to central insulin and leptin resistance [12]
Summary
There is a growing body of evidence showing that the nutritional environment during early life may have later effects on the propensity to suffer from obesity and its related metabolic pathologies [1,2] In this sense, maternal prenatal malnutrition has been described to have long term consequences on offspring metabolic energy regulatory systems, and has been associated with obesity in adult rats and humans [3,4]. Most of the studies in this sense have addressed the effects of severe caloric restriction, which is known to result in marked fetal growth retardation, whereas, to the best of our knowledge, the lasting effects of moderate, less severe caloric restriction during gestation on energy homeostasis in both male and female offspring have not been directly studied. We consider this grade of restriction better fits within the normal range of human intake, and can be more relevant to human diet health
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