Developmental gene × environment interactions affecting systems regulating energy homeostasis and obesity

Most human obesity is inherited as a polygenic trait which is largely refractory to medical therapy because obese individuals avidly defend their elevated body weight set-point. This set-point is mediated by an integrated neural network that controls energy homeostasis. Epidemiological studies suggest that perinatal and pre-pubertal environmental factors can promote offspring obesity. Rodent studies demonstrate the important interactions between genetic predisposition and environmental factors in promoting obesity. This review covers issues of development and function of neural systems involved in the regulation of energy homeostasis and the roles of leptin and insulin in these processes, the ways in which interventions at various phases from gestation, lactation and pre-pubertal stages of development can favorably and unfavorably alter the development of obesity n offspring. These studies suggest that early identification of obesity-prone humans and of the factors that can prevent them from becoming obese could provide an effective strategy for preventing the world-wide epidemic of obesity.