Critical Importance of the Perinatal Period in the Development of Obesity

Abstract

Epidemiological studies suggest that maternal undernutrition, obesity,and diabetes during gestation and lactation can all produce obesity inoffspring. Animal models provide a means of assessing the independentconsequences of altering the pre- versus postnatal environments on avariety of metabolic, physiologic, and neuroendocrine functions thatlead to the development of offspring obesity, diabetes, hypertension,and hyperlipidemia. During the gestational period, maternalmalnutrition, obesity, type 1 and type 2 diabetes, and psychological,immunological, and pharmacological stressors can all promote offspringobesity. Normal postnatal nutrition can sometimes reduce the adverseimpact of some of these prenatal factors but may also exacerbate thedevelopment of obesity and diabetes in offspring of dams that weremalnourished during gestation. The genetic background of the individualis also an important determinant of outcome when the perinatalenvironment is perturbed. Individuals with an obesity-prone genotype aremore likely to be adversely affected by factors such as maternal obesityand high-fat diets. Many perinatal manipulations are associated withreorganization of the central neural pathways that regulate food intake,energy expenditure, and storage in ways that enhance the development ofobesity and diabetes in offspring. Both leptin and insulin have strongneurotrophic properties so that either an excess or an absence of eitherduring the perinatal period may underlie some of these adversedevelopmental changes. Because perinatal manipulations can permanentlyand adversely alter the systems that regulate energy homeostasis, itbehooves us to gain a better understanding of the factors during thisperiod that promote the development of offspring obesity as a means ofstemming the tide of the emerging worldwide obesity epidemic.