V. Daniel Castracane, Ph.D.

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LEPTIN

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ENDOCRINE UPDATES

Shlomo Melmed, M.D., Series Editor

J.A. Fagin (ed.): Thyroid Cancer. 1998. ISBN: 0-7923-8326-5 J.S. Adams and B.P. Lukert (eds.): Osteoporosis: Genetics, Prevention and Treatment. 1998. ISBN: 0-7923-8366-4.

B.-A. Bengtsson (ed.): Growth Hormone. 1999. ISBN: 0-7923-8478-4 C. Wang (ed.): Male Reproductive Function. 1999. ISBN: 0-7923-8520-9 B. Rapoport and S.M. McLachlan (eds.): Graves' Disease:

Pathogenesis and Treatment. 2000. ISBN: 0-7923-7790-7.

W. W. de Herder (ed.): Functional and Morphological Imaging of the Endocrine System. 2000. ISBN 0-7923-7923-9

H.G. Burger (ed.): Sex Hormone Replacement Therapy. 2001.

ISBN 0-7923-7965-9

A. Giustina (ed.): Growth Hormone and the Heart. 2001.

ISBN 0-7923-7212-3

W.L. Lowe, Jr. (ed.): Genetics of Diabetes Mellitus. 2001.

ISBN 0-7923-7252-2

J.F. Habener and M.A. Hussain (eds.): Molecular Basis of Pancreas Development and Function. 2001. ISBN 0-7923-7271-9

N. Horseman (ed.): Prolactin. 2001. ISBN 0-7923-7290-5 M. Castro (ed.): Transgenic Models in Endocrinology. 2001 ISBN 0-7923-7344-8

R. Bahn (ed.): Thyroid Eye Disease. 2001. ISBN 0-7923-7380-4 M.D. Bronstein (ed.): Pituitary Tumors in Pregnancy

ISBN 0-7923-7442-8

K. Sandberg and S.E. Mulroney (eds.): RNA Binding Proteins:

New Concepts in Gene Regulation. 2001. ISBN 0-7923-7612-9 V. Goffin and P. A. Kelly (eds.): Hormone Signaling. 2002 ISBN 0-7923-7660-9

M. C. Sheppard and P. M. Stewart (eds.): Pituitary Disease. 2002 ISBN 1-4020-7122-1

N. Chattopadhyay and E.M. Brown (eds.): Calcium-Sensing Receptor.

2002. ISBN 1-4020-7314-3

H. Vaudry and A. Arimura (eds.): Pituitary Adenylate Cyclase- Activating Polypeptide. 2002. ISBN 1-4020-7306-2

R.C. Gaillard (ed.): The ACTH AXIS: Pathogenesis, Diagnosis and Treatment. 2003. ISBN 1-4020-7563-4

P. Beck-Peccoz (ed.): Syndromes of Hormone Resistance on the Hypothalamic- Pituitary-Thyroid Axis. 2004. ISBN 1-4020-7807-2

E. Ghigo (ed.): Ghrelin. 2004. ISBN 1-4020-7770-X

C.B. Srikant (ed.): Somatostatin. 2004. ISBN 1-4020-7799-8

V.D. Castracane and M.C. Henson (eds.): Leptin. 2006. ISBN 0-387-31415-6 G. Bray and D. Ryan (eds.): Obesity and the Metabolic Syndrome. 2006.

ISBN 0-387-32163-2

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LEPTIN

edited by

V. Daniel Castracane, Ph.D.

Professor Emeritus

Texas Tech University School of Medicine Lubbock, Texas, USA

Michael C. Henson, Ph.D.

Professor and Head

Department of Biological Sciences Purdue University Calumet

Hammond, Indiana, USA

^ Spri ringer

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V. Daniel Castracane, PhD Michael C. Henson, PhD

Director of Laboratory Operations Dept. of Obstetrics and Gynecology Foundation for Blood Research School of Medicine

P. O. Box 190 Tulane University Health Sciences Center Scarborough, ME, USA New Orleans, LA, USA

LEPTIN

Library of Congress Control Number: 2005938989

ISBN-10: 0-387-31415-6 e-ISBN-10: 0-387-31416-4 ISBN-13: 978-0387-31415-0 e-ISBN-13: 978-0387-31416-7 Printed on acid-free paper.

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.

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The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed in the United States of America.

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Dedication

This volume is dedicated to my parents, wiio fostered the desire for education, and to a long list of mentors and colleagues who have contributed to my scientific development; but especially to Catherine, Teresa and Jennifer who serve as the continuing inspiration of my life.

VDC

This volume is dedicated to my parents, mentors, trainees and collaborators, and to my colleagues of the Gulf coast, many of whom lost so much in the hurricanes of 2005; but especially to Libby, Kate, Rachel and Chris, who continue to make everything worthwhile.

MCH

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CONTRIBUTORS

Rexford S. Ahima, MD, PhD Associate Professor

University of Pennsylvania Scliool of Medicine Department of Medicine, Division of Endocrinology,

Diabetes and Metabolism Philadelphia, PA 19104 Delia-Marina Alexe, MD

Research Associate

Department of Hygiene and Epidemiology Athens University Medical School

Athens, Greece C. Richard Barb, PhD

Research Leader USDA-ARS

Animal Physiology Research Unit Russell Research Center

Athens, GA 30604-5677 Lauren N. Bell, BS

Department of Integrative and Cellular Physiology Department of Medicine

Lidiana University School of Medicine Indianapolis, IN 46202

Joao Vicente Busnello, MD Neuropsychiatric Institute

David Geffen School of Medicine University of California, Los Angeles Los Angeles, CA

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V. Daniel Castracane, PhD Professor Emeritus

Department of Obstetrics and Gynecology Texas Tech University School of Medicine Lubbock, TX 79430

Robert V. Considine, PhD

Department of Cellular and Integrative Physiology Department of Medicine

Indiana University School of Medicine Indianapolis, IN 46202

Marcelo L. Correia, MD

Post -doctoral Research Fellow

Specialized Center for Research in Hypertension Genetics Department of Internal Medicine

University of Iowa Iowa City, lA 52242 AlexM. DePaoIi,MD

Director of Global Development Amgen Pharmaceuticals

Thousand Oaks, CA 91320

Veronica De Rosa, PhD Research Associate

Gruppo di ImmunoEndocrinologia

Istituto di Endocrinologia e Oncologia Sperimentale Consiglio Nazionale delle Ricerche

c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare Universita di Napoli "Federico 11"

Via S. Pansini, 5 80131 Napoli, Italy

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I. SadafFarooqi,MD,PhD

Department of Clinical Biochemistry University of Cambridge

Addenbrooke's Hospital Cambridge CB2 2QQ, UK Gary J. Hausman, PhD

Research Physiologist USDA, ARS

Animal Physiology Research Unit Russell Research Center

Athens, GA 30605 William G. Haynes, MD

Professor of Internal Medicine

Specialized Center for Research in Hypertension Genetics Department of Internal Medicine

University of Iowa Iowa City, lA 52242 Michael C. Henson, PhD

Professor and Head

Department of Biological Sciences Purdue University Calumet

Hammond, IN 46323-2094 Affiliate Scientist

Tulane National Primate Research Center Covington, LA 70433

Malaka B. Jackson, MD Endocrinology Fellow

University of Pennsylvania School of Medicine Children's Hospital of Philadelphia

Philadelphia, PA 19104

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Julio Licinio, MD

Professor of Psychiatry and Biobehavioral Sciences and Medicine/Endocrinology

Director, Center for Pharmacogenomics and Clinical Pharmacology

Semel Institute of Neuroscience and Human Behavior David Geffen School of Medicine at UCLA

Los Angeles, CA 90095-1761 Giuseppe Matarese, MD, PhD

Gruppo di ImmunoEndocrinoIogia

Via S. Pansini, 5 80131 Napoli, Italy Jehangir Mistry, PhD

Vice President, Research and Development Linco Research, Inc

St Charles, MO 63304 Elif A. Oral, MD

Division of Metabolism, Endocrinology and Diabetes Department of Internal Medicine

University of Michigan School of Medicine Ann Arbor, MI 48109 Eleni Petridou, MD, MPH

Professor of Preventive Medicine and Epidemiology Department of Hygiene and Epidemiology

Athens University Medical School Athens, Greece

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Claudio Procaccini, PhD Research Associate

Gruppo di ImmunoEndocrinologia

Via S. Pansini, 5 80131 Napoli, Italy Kamal Rahmouni, PhD

Assistant Professor

Specialized Ceiater for Research in Hypertension Genetics Department of Internal Medicine

University of Iowa Iowa City, lA 52242 Timothy G. Ramsay, PhD

Research Physiologist USD A, ARS, ANRI

Growth Biology Laboratory Beltsville, MD 20705-2350 Robert E. Ratner, MD

Vice President for Scientific Affairs MedStar Research Institute

Hyattsville, MD 20783 Luciana Ribeiro, MD, PhD

Neuropsychiatric Institute

David Geffen School of Medicine University of California, Los Angeles Los Angeles, California, USA

Abhiram Sahu, PhD

Department of Cell Biology and Physiology University of Pittsburgh School of Medicine Pittsburgh, PA 15261-0001

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Laura C. Schulz, PhD Postdoctoral Fellow Biology Department Boston University

Boston, MA 02215-2406 Shu Takeda, MD

Department of Orthopedics

Tokyo Medical and Dental University Tokyo,Japan

Asha M. Thomas-Geevarghese, MD MedStar Research Institute Hyattsville, MD 20783 Eric P. Widmaier, PhD

Professor

Biology Department Boston University

Boston, MA 02215-2406 Ma-Li Wong, MD

Neuropsychiatric Institute

David Geffen School of Medicine University of California, Los Angeles Los Angeles, California, USA

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PREFACE

The discovery of leptin by Friedman and his colleagues in 1994 was a seminal discovery in the study of metabolism, providing a new tool to study energy expenditure and appetite regulation. Early studies actively investigated many aspects of metabolism, obesity, and diabetes but it was soon evident that leptin was much more than a metabolic hormone. Today leptin, with almost 11,000 reports in the world's literature, is recognized to be important in many areas of physiology with strong suggestions for involvement in clinical conditions as well. Leptin, of course, remains of great interest in obesity and diabetes but other, previously unimagined, areas are now in the realm of leptin physiology. Perhaps leptin and its involvement in many areas of reproductive physiology may be of greatest interest outside of obesity, but other physiological arenas are becoming increasingly involved in the broader understanding of leptin and its pleiotropic functions. These areas include cardiovascular disease, bone physiology, immune regulation, and even cancer and genetics.

Clinical trials have suggested other areas of leptin pharmaceutical potential beyond the original promise of obesity management. These topics and others, for the first time, have been collected in one volume as the first comprehensive review of leptin and its many actions. This area will continue to increase and is now compounded by new endocrine factors that have been elucidated in the wake of leptin's explosion onto the physiological scene. The future seems promising for an increased physiological understanding and the development of clinical applications. This volume will serve as the basis for understanding the past and present of leptin, and to indicate where the future direction of leptin may lead.

V. Daniel Castracane, PhD Michael C. Henson, PhD

V. Daniel Castracane, Ph.D.

LEPTIN

LEPTIN

edited by

V. Daniel Castracane, Ph.D.

Professor Emeritus

Texas Tech University School of Medicine Lubbock, Texas, USA

Michael C. Henson, Ph.D.

Professor and Head

Department of Biological Sciences Purdue University Calumet

Hammond, Indiana, USA

^ Spri ringer

Dedication

CONTENTS

CONTRIBUTORS

PREFACE