Metabolic Programming Due to Alterations in Nutrition in the Immediate Postnatal Period1–3

Abstract

Altered nutritional experiences such as undernutrition, overnutrition, and modified milk formula in the immediate postnatal life via the phenomenon of metabolic programming have been identified as one of the components in the etiology of metabolic syndrome. We have developed a rat model in which an altered dietary experience in the form of a high-carbohydrate (HC) milk formula in the immediate postnatal life of rat pups results in chronic hyperinsulinemia and adult-onset obesity in these rats. The HC dietary modification causes functional alterations in pancreatic islets and the hypothalamus during the period of the dietary modification. These early adaptations in islets (supporting hyperinsulinemia) and the hypothalamus (supporting hyperphagia and increased body weight gain) persist in the postweaning period despite withdrawal of the HC milk formula at the time of weaning. In female rat pups receiving the HC milk formula, metabolic programming effects translate into an adverse (hyperinsulinemic, hyperleptinemic, and obese) intrauterine environment during pregnancy, causing spontaneous transfer of the maternal phenotype to the progeny (generational effect). Our results suggest that alterations in feeding practices for babies (early introduction of cereals, fruits, etc.) and babies born to obese/hyperinsulinemic mothers may be contributing factors for the obesity epidemic prevalent in developed and developing countries.