title: 20 years of leptin: human disorders of leptin action.
abstract: The discovery of leptin has provided a robust framework upon which our current understanding of the mechanisms involved in energy homeostasis has been built. In this review, we describe how the identification of humans with mutations in the genes encoding leptin and the leptin receptor and the characterisation of the associated clinical phenotypes have provided insights into the role of leptin-responsive pathways in the regulation of eating behaviour, intermediary metabolism and the onset of puberty. Importantly, administration of recombinant human leptin in leptin deficiency represents the first mechanistically based targeted therapy for obesity and has provided immense clinical benefits for the patients concerned. In subsequent years, we and others have shown that human obesity can result from a multiplicity of defects in the pathways downstream of leptin signalling within the brain.
authors.affiliation: MRC Metabolic Diseases UnitMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK isf20@cam.ac.uk.
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.affiliation: MRC Metabolic Diseases UnitMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000172:deficiency / Q000235:genetics* / Q000627:therapeutic use; D008957:Models, Genetic; D009154:Mutation; D009765:Obesity / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
keywords: leptin; obesity; receptors; signal transduction