A maternal low protein diet programs glucose and fatty acid metabolism differentially in adult male and female mouse offspring

Abstract

Nutritional conditions during fetal life can influence the risk to develop the metabolic syndrome in adult life (‘metabolic programming’). We aimed to establish a mouse model of metabolic programming focusing on the effects of a maternal low protein diet during gestation on glucose and lipid metabolism in the adult offspring. Pregnant C57BL/6J mice received a control or a low protein diet throughout gestation. Offspring received a low fat diet or a high fat diet from 6–22 weeks of age. Glucose metabolism was studied with a whole‐body‐glucose test using [6,6‐2H]‐glucose. Hepatic gene expression was characterized by microarray. Maternal low‐protein‐diet did not affect glucose metabolism in male offspring. Female offspring from normal‐protein fed dams was relatively resistant to diet‐induced metabolic dysregulation. Maternal low‐protein‐diet during gestation led to deteriorated insulin sensitivity upon high‐fat feeding in female offspring. Microarray analyses showed a sex‐specific effect of the maternal diet. We conclude that, in mice, maternal protein restriction during gestation does not change the glucose response to a high fat diet in male offspring. However, it changes fatty acid and glucose metabolism in female offspring in such a way that it resembles male metabolism. Supported by the Netherlands Heart Foundation, grant 2004T048.