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I Sadaf Farooqi MRC Metabolic Diseases Unit, Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

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Stephen O'Rahilly MRC Metabolic Diseases Unit, Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

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Discovery of mutations in leptin and the leptin receptor in humans Early studies carried out in obese humans showed that leptin mRNA concentrations in adipose tissue and serum leptin concentrations correlated positively and very closely with the

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Margaret B Allison Departments of Internal Medicine, and Molecular and Integrative Physiology, University of Michigan, 1000 Wall Street, 6317 Brehm Tower, Ann Arbor, Michigan 48105, USA

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Martin G Myers Jr Departments of Internal Medicine, and Molecular and Integrative Physiology, University of Michigan, 1000 Wall Street, 6317 Brehm Tower, Ann Arbor, Michigan 48105, USA

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important and widely studied players in the control of energy balance is the hormone leptin ( Friedman & Halaas 1998 , Elmquist et al . 2005 ). Leptin was discovered by Zhang et al . (1994) . Defects in leptin production underlie the massive obesity

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Jeffrey Friedman Rockefeller University, Box 305, 1230 York Avenue, New York, New York 10065, USA

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& Halaas 1998 ). While some of the features of this new hormonal system were predicted at the time, others were not. Science seldom proceeds in a straight line, and the field spawned by the identification of leptin and other genes that cause obesity is no

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Michael Rosenbaum Division of Molecular Genetics, Departments of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University, Russ Berrie Medical Science Pavilion, 6th Floor, 1150 St Nicholas Avenue, New York, New York 10032, USA

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Rudolph L Leibel Division of Molecular Genetics, Departments of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University, Russ Berrie Medical Science Pavilion, 6th Floor, 1150 St Nicholas Avenue, New York, New York 10032, USA

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(1973) . Efforts to identify the ob and db gene products then began in earnest ( Leibel et al . 1993 ). Coleman's ‘satiety factor’ of course proved to be leptin ( Zhang et al . 1994 ). Leptin repletion of congenitally leptin-deficient rodents and

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Sharon H Chou Section of Adult and Pediatric Endocrinology, Division of Endocrinology, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637, USA

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Christos Mantzoros Section of Adult and Pediatric Endocrinology, Division of Endocrinology, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637, USA
Section of Adult and Pediatric Endocrinology, Division of Endocrinology, Section of Endocrinology, Diabetes and Metabolism, The University of Chicago, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637, USA

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Introduction In 1974, Frisch proposed that the ability to reproduce requires a certain threshold of body fat to serve as the minimal store of energy necessary for ovulation, menstruation, and intended pregnancy ( Frisch & McArthur 1974 ). Leptin

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Frank Peelman
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Lennart Zabeau
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Kedar Moharana Department of Medical Protein Research, Unit for Structural Biology, Faculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium

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Savvas N Savvides Department of Medical Protein Research, Unit for Structural Biology, Faculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium

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Jan Tavernier
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Introduction Leptin and the leptin receptor (LR) are essential components in the complex genetic wiring diagram underlying energy homeostasis and body weight. The hormone is now known to participate in a wide range of biological functions including

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M Matheny Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA

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K Y E Strehler Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA

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M King Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA
Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA

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N Tümer Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA
Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA

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P J Scarpace Department of Pharmacology and Therapeutics, Department of Veterans Affairs, College of Medicine, University of Florida, PO Box 100267, Gainesville, Florida 32610, USA

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Introduction The adipocyte-derived hormone, leptin, regulates appetite and energy expenditure through its action in the hypothalamus and other brain sites ( Li 2011 ). Our previous studies involving central leptin gene delivery (leptin

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Farid F Chehab Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94132, USA

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critical periods is an essential component of normal physiology. In this review, we will address the leptin-mediated effects and associated mechanisms that pertain to the accumulation of adipose mass at critical times during the reproductive events of a

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Saadia Basharat
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Jennifer A Parker Division of Diabetes, University College London, Brunel University, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital Campus, 6th Floor, Commonwealth Building, Du Cane Road, London W12 0NN, UK

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Kevin G Murphy
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Stephen R Bloom
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Julia C Buckingham Division of Diabetes, University College London, Brunel University, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital Campus, 6th Floor, Commonwealth Building, Du Cane Road, London W12 0NN, UK

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Christopher D John
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a context in which any additional inflammatory stimulus results in an exaggerated inflammatory response ( Vachharajani 2008 ). The adipose tissue-derived hormone leptin has a well-characterised role in energy homoeostasis, but has also been suggested

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Amrutha Bagivalu Lakshminarasimha Institute of Zoology, University of Cologne, Cologne, Germany

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Patrick Page-McCaw Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

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Diana Möckel Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

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Felix Gremse Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
Gremse-IT GmbH, Aachen, Germany

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Maximilian Michel Institute of Zoology, University of Cologne, Cologne, Germany

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(db/db) alleles led to the milestone discovery of the leptin system. The hormone leptin ( ob gene) is released by adipose tissue in proportion to fat stores. Leptin signals the status of peripheral adipose stores to the brain, where it is received by

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