Metabolic programming in the immediate postnatal life

Abstract

The metabolic programming effects of nutritional modifications in the immediate postnatal life are increasingly recognized to independently contribute to the development of metabolic syndrome in later life. Adjustment of litter size in rodents has been used to induce either under- or overnourishment in the immediate postnatal life of the offspring. While undernourishment led to growth retardation in the offspring, overnourishment produced increased body weight gains, hyperinsulinemia and hyperleptinemia. Overnourishment during the suckling period induced several adaptations in the energy circuitry in the hypothalamus of the offspring predisposing them for the onset of obesity later in life. Another approach for a nutritional modification in the immediate postnatal period is the artificial rearing of newborn rat pups on a high-carbohydrate (HC) milk formula without changes in the total calorie availability. Hyperinsulinemia, immediately evident in the HC pups, persisted in the post-weaning period even after withdrawal of the HC milk. Significant alterations in pancreatic islets supported chronic hyperinsulinemia in the HC rats. Alterations in the gene expression of hypothalamic neuropeptides predisposing to hyperphagia were evident during the period of the HC dietary modification. The persistence of these hypothalamic adaptations supported the obese phenotype in adult HC rats. A transgenerational effect gave rise to the development of chronic hyperinsulinemia and adult-onset obesity in the offspring of the HC female rats. Other studies have shown that lactation by a diabetic, obese or malnourished mother resulted in predisposition for the onset of metabolic disorders in the offspring. These observations from animal studies on the metabolic programming effects due to altered nutritional experiences in the immediate postnatal life strongly suggest that altered feeding practices for infants (formula feeding and early introduction of infant foods) could contribute to the rising incidence of overweight/obesity in children and adults.

Fig. 1.

The various animal models for altered nutritional experiences in the immediate postnatal life. The changes in the quality or quantity of milk received by the offspring are also indicated.

Fig. 2.

The possible mechanisms supporting the development of obesity/metabolic syndrome in the SL model. It is postulated that the altered hormonal levels observed during the suckling period ‘malprogram’ the energy homeostatic mechanism in the SL (overnourished) rats resulting in hyperphagia and increased body weight gains in the post-weaning period and development of obesity and metabolic syndrome in adulthood. The thickness of arrows outside the boxes indicates the relative contributions to metabolic programming. The shorter arrows in the boxes indicate the direction of the changes.

Fig. 3.

A representation of the responses to the HC milk formula and the possible cross-talk between the target organs, which support the development of the obesity/metabolic syndrome in the post-weaning period. The thickness of the arrows indicates the relative contribution to metabolic programming. The shorter arrows in the boxes indicate the direction of the changes. ANS/PNS/SNS = Autonomic/parasympathetic/sympathetic nervous system.

Fig. 4.

Based on animal studies and observations in humans, malprogramming and nutritional alterations during early postnatal life could significantly increase the risk for development of metabolic disorders in adulthood. ANS = Autonomic nervous system.