Leptin and the treatment of obesity: its current status

Abstract

Leptin, the protein product of the ob gene, is primarily an adipocyte-secreted hormone, whose functional significance is rapidly expanding. Although early research efforts were focused on defining leptin's role in reversing obesity in rodents, there is now substantial evidence indicating that its influence extends to several hypothalamic-pituitary-endocrine axes, including gonadal, adrenal, thyroid, growth hormone, and pancreatic islets. A role for leptin in hematopoiesis, angiogenesis, immune function, osteogenesis, and wound healing has also been documented. The results of recent clinical trials with recombinant human leptin indicated that its effectiveness in restoring energy balance and correcting obesity-related endocrinopathies in genetically obese rodent models extended only partially to the management of human obesity. New efforts in drug development have focused on leptin-related synthetic peptide agonists as potential anti-obesity pharmacophores.