Role of leptin in early metabolic programming

Abstract

Experimental studies in rodents have highlighted the relationship between early postnatal events, undernutrition during pregnancy and/or lactation and the subsequent development of metabolic syndrome, a phenomenon termed developmental programming. However, appearance of metabolic syndrome is dependent not only on prenatal or postnatal predisposition but also on type of nutrition throughout the life cycle. Those experimental findings have been supported by epidemiological data in humans, born to mothers who suffered undernutrition during pregnancy. Leptin is likely involved is such programming and maintaining a critical leptin level during development may allow normal maturation of tissues and pathways involved in metabolic homeostasis, reversing the undesired effects. Leptin disruption during a critical neonatal or prenatal window is sufficient to permanently alter long-term metabolic regulation. Thus, in rodents (in the early postnatal phase), and likely in other species such as primates, and including humans (in the prenatal period), leptin plays a major role in the development of brain circuits which affect future developmental programming of metabolic disease. As postnatal nutritional or therapeutic intervention can ameliorate the consequences of developmental malprogramming, use of leptin as an additive to milk in infant formula which, in contrast to maternal milk, which is devoid of this protein, has been suggested. Alternatively, identification of potential factors elevating leptin levels in maternal milk may also be beneficial. In conclusion, the present data highlight the importance of leptin in the developmental induction of metabolic disease and offer exciting new strategies for therapeutic intervention, by either maternal or neonatal intervention or targeted nutritional manipulation in postnatal life. Adipobiology 2009; 1: 27-34.