Leptin and Leptin Antagonists

The discovery of leptin, the obese (ob) gene product which is not expressed as a functional protein in ob/ob mice, focused the scientific community’s attention on its role as an anorexic hormone involved in the negative regulation of food intake. Almost 14 years after this breakthrough discovery and over 14,000 leptin-related publications later, leptin is now known to participate in a wide range of biological functions that include, in addition to its early envisaged function as an adipostat, glucose metabolism, glucocorticoid synthesis, CD4+ T-lymphocyte proliferation, cytokine secretion, phagocytosis, hypothalamic-pituitary-adrenal axis regulation, reproduction, cardiovascular pathology, bone formation, apoptosis and angiogenesis. In short, it is now well-documented that leptin acts like a cytokine hormone with many pleiotropic effects. Furthermore, in recent years, it has become more and more apparent that many of leptin’s effects are acquired not only through its central action, but also through its systemic action on a peripheral level. This book focuses mainly on the relatively novel aspects of leptin’s actions. Leptin’s involvement in early postnatal imprinting has led to new insight into developmental programming. This highly novel aspect of leptin’s action is reviewed extensively in the final chapter of this book by the Auckland group, Vickers, Krechowec, Gluckman and Breier. In the last five years, it has been shown that at least in rodents, leptin acts as an important neurotrophic factor promoting the early postnatal maturation of neural pathways within the hypothalamus. The authors review experimental evidence, originating largely from their own work, which shows that therapeutic intervention with leptin in the rodents’ early postnatal life can potentially reverse or substantially ameliorate the consequences of developmental malprogramming, and that this effect is highly influenced by both gender and postnatal diet.