The normal programmed development of a multicellular organism from the germ cell is a synchronized series of events driven by genetic instructions acquired during conception. During the early critical periods in life the organism also has the ability to respond to environmental situations that are alien to normal development by adaptations at the cellular, molecular, and biochemical levels. Such early adaptations to a nutritional stress/stimulus permanently change the physiology and metabolism of the organism and continue to be expressed even in the absence of the stimulus/stress that initiated them, a process termed "metabolic programming" (1). A brief summary of the findings from human epidemiological and animal studies is presented below in support of the concept of metabolic programming induced by nutritional experiences during critical periods in development with consequences later in adulthood. For detailed accounts the reader is referred to excellent reviews on this subject (2-5). This minireview will focus on metabolic programming with reference to a novel rat model developed in our laboratory. Evidence for Metabolic Programming from Human Epidemiological DataExtensive epidemiological findings indicate that metabolic programming occurs in humans. Barker (6) was the first to suggest from epidemiological studies that the disproportionate size of the newborn resulting from maternal malnutrition correlated with an increased risk for adverse health outcomes (type II diabetes, hypertension, and cardiovascular diseases) later in adult life. These primary observations resulted in the now widely recognized "fetal origins" hypothesis emphasizing the importance of adequate maternal nutrition during pregnancy (4). Evidence for Metabolic Programming in AnimalsNutritional programming has been demonstrated in animal studies. In pioneering studies with rodents, McCance (7) demonstrated by adjusting litter size that the quantity of food consumed during early periods of postnatal life has long term consequences on growth. The consequences of maternal malnutrition induced by either a low protein diet or caloric restriction during gestation and lactation cause major changes in the structure and function of several organs in the offspring. Pregnant rats fed a low protein diet produced pups with alterations in pancreatic islets (8, 9). These include reduced islet vascularization, ␤ cell proliferative capacity, and islet size with rightward shift (decreased sensitivity) in glucose-stimulated insulin secretion and altered sensitivity to insulin in muscle (8, 9). Furthermore, hypothalamic nuclei are malformed in these weanling rats; this is accompanied by reduced vascularization of the cerebral cortex in the progeny (10). Metabolic capacities of the liver, muscle, and adipose tissue are compromised by maternal protein restriction during gestation and lactation with adverse adult onset outcomes (11). Elevated insulin concentrations during critical periods of development, as occurs perinatally in the offspring of gestationally dia...

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