Developmental programming of energy balance and its hypothalamic regulation.

Developmental programming is an important physiological process that allows different phenotypes to originate from a single genotype. Through plasticity in early life, the developing organism can adopt a phenotype (within the limits of its genetic background) that is best suited to its expected environment. In humans, together with the relative irreversibility of the phenomenon, the low predictive value of the fetal environment for later conditions in affluent countries makes it a potential contributor to the obesity epidemic of recent decades. Here, we review the current evidence for developmental programming of energy balance. For a proper understanding of the subject, knowledge about energy balance is indispensable. Therefore, we first present an overview of the major hypothalamic routes through which energy balance is regulated and their ontogeny. With this background, we then turn to the available evidence for programming of energy balance by the early nutritional environment, in both man and rodent models. A wealth of studies suggest that energy balance can indeed be permanently affected by the early-life environment. However, the direction of the effects of programming appears to vary considerably, both between and within different animal models. Because of these inconsistencies, a comprehensive picture is still elusive. More standardization between studies seems essential to reach veritable conclusions about the role of developmental programming in adult energy balance and obesity.