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Fatty Acid and Lipotoxicity in Obesity and Diabetes (Novartis Foundation Symposium 286) PDF

221 Pages·2008·2.65 MB·English
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Fatty Acids and Lipotoxicity in Obesity and Diabetes: Novartis Foundation Symposium 286, Volume 286. Edited by Gregory Bock and Jamie Goode Copyright  Novartis Foundation 2007. ISBN: 978-0-470-05764-3 FATTY ACIDS AND LIPOTOXICITY IN OBESITY AND DIABETES The Novartis Foundation is an international scientifi c and educational charity (UK Registered Charity No. 313574). Known until September 1997 as the Ciba Foundation, it was established in 1947 by the CIBA company of Basle, which merged with Sandoz in 1996, to form Novartis. The Foundation operates independently in London under English trust law. It was formally opened on 22 June 1949. The Foundation promotes the study and general knowledge of science and in particular encourages international co-operation in scientifi c research. To this end, it organizes internationally acclaimed meetings (typically eight symposia and allied open meetings and 15–20 discussion meetings each year) and publishes eight books per year featuring the presented papers and discussions from the symposia. Although primarily an operational rather than a grant-making foundation, it awards bursaries to young scientists to attend the symposia and afterwards work with one of the other participants. The Foundation’s headquarters at 41 Portland Place, London W1B 1BN, provide library facilities, open to graduates in science and allied disciplines. Media relations are fostered by regular press conferences and by articles prepared by the Foundation’s Science Writer in Residence. The Foundation offers accommodation and meeting facilities to visiting scientists and their societies. Information on all Foundation activities can be found at http://www.novartisfound.org.uk As one of China’s most renowned universities, Tsinghua is an important center of learning in China for fostering talent and scientifi c research. The centre area of the campus of Tsinghua University is situated on former imperial gardens of the Qing Dynasty. Tsinghua University was founded in 1911, originally under the name of Tsinghua Xuetang, as a preparatory school for students who would be sent by the government to study in the United States. It was renamed Tsinghua School in 1912. The university section was founded in 1925. The name National Tsinghua University was adopted in 1928 and in 1929 the Tsinghua Research Institute was set up. The Resistance War against the Japanese Invasion in 1937 forced Tsinghua to move to Kunming, where it formed, with Peking University and Nankai University, Southwest Associated University. In 1946, the University was moved back to its original location in Peking. In 1952, Tsinghua University became a polytechnic institution with an engineering focus known as China’s ‘cradle of engineers’. Since 1978, with the resumption of departments in science, economics, management and the humanities, Tsinghua University has fl ourished in many fi elds besides engineering. Tsinghua is rapidly developing into a comprehensive research university with faculties in science, engineering, humanities, law, medicine, history, philosophy, economics, management, education, and art. Novartis Foundation Symposium 286 FATTY ACIDS AND LIPOTOXICITY IN OBESITY AND DIABETES Copyright © Novartis Foundation 2007 Published in 2007 by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester PO19 8SQ, UK National 01243 779777 International (+44) 1243 779777 e-mail (for orders and customer service enquiries): [email protected] Visit our Home Page on http://www.wileyeurope.com or http://www.wiley.com All Rights Reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to permreq@ wiley.co.uk, or faxed to (+44) 1243 770620. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the Publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Other Wiley Editorial Offi ces John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstr. 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons Canada Ltd, 6045 Freemont Blvd, Mississauga, Ontario, Canada L5R 4J3 Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Novartis Foundation Symposium 286 x + 212 pages, 34 fi gures, 2 tables Anniversary Logo Design: Richard J Pacifi co British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 978-0-470-05764-3 Typeset in 10.5 on 12.5 pt Garamond by SNP Best-set Typesetter Ltd., Hong Kong Printed and bound in Great Britain by T. J. International Ltd, Padstow, Cornwall. This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production. Contents Symposium on Fatty acids and lipotoxicity in obesity and diabetes, held at Tsinghua University, Beijing, China, 17–19 October 2006 Editors: Gregory Bock (Organizer) and Jamie Goode This symposium is based on a proposal made by Peng Li Bruce M. Spiegelman Chair’s introduction 1 Bruce M. Spiegelman Transcriptional control of energy homeostasis through the PGC1 coactivators 3 Discussion 6 Stephen O’Rahilly Human obesity and insulin resistance: lessons from experiments of nature 13 Discussion 20 Deborah M. Muoio and Timothy R. Koves Lipid-induced metabolic dysfunction in skeletal muscle 24 Discussion 38 Alan D. Attie, Matthew T. Flowers, Jessica B. Flowers, Albert K. Groen, Folkert Kuipers and James M. Ntambi Stearoyl-CoA desaturase defi ciency, hypercholesterolaemia, cholestasis and diabetes 47 Discussion 54 Karen Reue The role of lipin 1 in adipogenesis and lipid metabolism 58 Discussion 68 David Carling The role of the AMP-activated protein kinase in the regulation of energy homeostasis 72 Discussion 81 Gökhan S. Hotamisligil Endoplasmic reticulum stress and infl ammation in obesity and type 2 diabetes 86 Discussion 94 v vi CONTENTS Ira Tabas, Tracie Seimon, Jerry Arellano, Yankun Li, Fabien Forcheron, Dongying Cui, Seongah Han, Chien-Ping Liang, Alan Tall and Domenico Accili The impact of insulin resistance on macrophage death pathways in advanced atherosclerosis 99 Discussion 109 Sandra Lobo and David A. Bernlohr Fatty acid transport in adipocytes and the development of insulin resistance 113 Discussion 121 Paul N. Black and Concetta C. DiRusso Vectorial acylation: linking fatty acid transport and activation to metabolic traffi cking 127 Discussion 138 Günther Daum, Andrea Wagner, Tibor Czabany, Karlheinz Grillitsch and Karin Athenstaedt Lipid storage and mobilization pathways in yeast 142 Discussion 151 John Zhong Li and Peng Li Cide proteins and the development of obesity 155 Discussion 159 General discussion I 162 Visualizing brown adipose tissue with FDG-PET 162 Takashi Kadowaki, Toshimasa Yamauchi, Naoto Kubota, Kazuo Hara and Kohjiro Ueki Adiponectin and adiponectin receptors in obesity-linked insulin resistance 164 Discussion 176 Gabriel Pascual, Amy L. Sullivan, Sumito Ogawa, Amir Gamliel, Valentina Perissi, Michael G. Rosenfeld and Christopher K. Glass Anti-infl ammatory and antidiabetic roles of PPARγ 183 Discussion 196 Final discussion 200 Nutrition, ageing and lipotoxicity 200 Index of contributors 204 Subject index 206 Participants Alan D. Attie Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA David A. Bernlohr University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA Paul N. Black Ordway Research Institute, Inc., 150 New Scotland Avenue, Albany, NY 12208, USA David Carling Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK Günther Daum Institut für Biochemie, Technische Universität Graz, Petersgasse 12/2, A-8010 Graz, Austria Diego De Mendoza Institute of Molecular and Cellular Biology of Rosario, CONICET, Universidad Nacional de Rosario, Suipacha 531, 2000-Rosario, Argentina Christopher K. Glass University of California San Diego, Department of Cellu- lar and Molecular Medicine, 9500 Gilman Drive, GPL Rm 217, La Jolla, CA 92093-0651, USA Xiao Han The Key Laboratory of Human Functional Genomics of Jiangsu Prov- ince, Nanjing Medical University, Nanjing 210029, People’s Republic of China Gökhan S. Hotamisligil Harvard School of Public Health, Department of Genetics and Complex Diseases, Building I, Room 205, 655 Huntington Avenue, Boston, MA 02115, USA Takashi Kadowaki Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan vii viii PARTICIPANTS Jae Bum Kim Department of Biological Sciences, Seoul National University, Bldg. 20-Rm. 109, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea Peng Li Department of Biological Sciences and Biotechnology, Tsinghua Univer- sity, Beijing, People’s Republic of China Xiaoying Li 197 Ruijin 2nd Road, Department of Endocrinology, Ruijin Hospi- tal, Shanghai 200025, People’s Republic of China Kan Liao Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, 320 Yueyang Rd., Shanghai 200031, People’s Republic of China Deborah M. Muoio Sarah W. Stedman Nutrition and Metabolism Center, and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Independence Park, Durham, NC 27704, USA Yi-Ming Mu Department of Endocrinology, Chinese PLA General Hospital, Fu Xing Road 28, HaiDian District, Beijing 100853, China Stephen O’Rahilly University of Cambridge, Department of Clinical Biochem- istry, Level 4, Laboratory Block, Box 232, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QR, UK Karen Reue Department of Human Genetics, Gonda Center 6506A, David Geffen School of Medicine at UCLA, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA Matthew Sabin (Novartis Foundation Bursar) Department of Endocrinology and Diabetes, Royal Children’s Hospital, Parkville 3052, Victoria, Australia Masayuki Saito Department of Nutrition, Graduate School of Nursing and Nutrition, Tenshi College, Sapporo 065-0013, Japan Yuguang Shi Department of Cellular and Molecular Physiology, Penn State Uni- versity School of Medicine, Hershey, PA 17033, USA Bruce M. Spiegelman (Chair) Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA Ira Tabas Columbia University, Department of Medicine, PH 8 East 105F, Division of Molecular Medicine, 630 West 168th Street, New York, NY 10032, USA PARTICIPANTS ix Robert Yang School of Biotechnology and Molecular Biosciences, University of New South Wales, Room 206, Biological Sciences Building, Sydney 2052, Australia Chen-Yu Zhang School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, People’s Republic of China

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The potential lipotoxic effect of accumulation of fatty acids in non-adipose tissues is thought to be a major component in the development of insulin resistance. Chronic exposure to high concentrations of free fatty acids in the blood affects pancreatic ? cell function, insulin secretion and lipid s
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