Early life programming in mice by maternal overnutrition: mechanistic insights and interventional approaches

Animal models have been indispensable in elucidating the potential causative mechanisms underlying the effects of maternal diet on offspring health. Of these, the mouse has been widely used to model maternal overnutrition and/or maternal obesity and to study its effects across one or more generations. This review discusses recent findings from mouse models, which resemble the human situation, i.e. overnutrition/obesity across pregnancy and lactation. It also highlights the importance of embryo transfer models in identifying critical developmental period(s) during which specific metabolic changes are programmed in the offspring. The mouse is also an excellent tool for maternal intervention studies aimed at elucidating the longer-term effects on the offspring and for defining possible maternal factors underling the programming of metabolic adversity in offspring. While knowledge of the mouse genome and the molecular tools available have allowed great progress to be made in the field, it is clear that we need to define if the effects on the offspring are mediated by maternal obesity per se or if specific components of the maternal metabolic environment are more important. We can then begin to identify at-risk offspring and to design more effective interventions for the mother and/or her child. This article is part of the theme issue 'Developing differences: early-life effects and evolutionary medicine'.