Developmental programming and adult obesity: the role of leptin

Abstract

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this 'programming' has generally been considered an irreversible change in developmental trajectory. Recent work has highlighted the importance of the hormone leptin during critical windows of development in the pathogenesis of programming related disorders. Maintaining a critical leptin level during development may allow the normal maturation of tissues and pathways involved in metabolic homeostasis and a period of relative hypo or hyperleptinemia may induce some of the metabolic adaptations which underlie developmental programming. Furthermore, nutritional or therapeutic intervention in postnatal life can ameliorate the consequences of developmental malprogramming and, at least in the rodent, developmental programming is potentially reversible by intervention with leptin late in the phase of developmental plasticity. Inappropriate growth during pregnancy or lactation can result in individuals with an increased risk of later obesity and related metabolic sequelae. Taken together, recent studies highlight the importance of leptin in disorders manifest as a consequence of developmental programming and offer exciting new strategies for therapeutic intervention, whether it be maternal or neonatal intervention or targeted nutritional manipulation in postnatal life.