Leptin as mediator of the effects of developmental programming

Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent upon early life conditions. In particular, altered maternal nutrition, including undernutrition and overnutrition, can lead to metabolic disorders in offspring characterised by obesity and leptin resistance. The adipokine leptin has received significant interest as a potential programming factor; alterations in the profile of leptin in early life are associated with altered susceptibility to obesity and metabolic disorders in adulthood. Maintenance of a critical leptin level during early development facilitates the normal maturation of tissues and signalling pathways involved in metabolic homeostasis. A period of relative hypo- or hyperleptinemia during this window of development will induce some of the metabolic adaptations which underlie developmental programming. However, it remains unclear whether leptin alone is a critical factor for the programming of obesity. At least in animal experimental studies, developmental programming is potentially reversible by manipulating the concentration of circulating leptin during a critical window of developmental plasticity and offers an exciting new approach for therapeutic intervention.