Hepatic De Novo Lipogenesis and Regulation of Metabolism
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1 Hepatic De Novo Lipogenesis and Regulation of Metabolism
2
3 James M. Ntambi Editor Hepatic De Novo Lipogenesis and Regulation of Metabolism
4 Editor James M. Ntambi Department of Biochemistry University of Wisconsin-Madison Madison, WI, USA ISBN DOI / ISBN (ebook) Library of Congress Control Number: Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (
5 Preface The liver is the largest solid vital organ in mammals that supports other organs in the body in some facet. Without a healthy liver, a person cannot survive. In the human it is located in the upper right quadrant of the abdomen, below the diaphragm. This book constitutes an effort to sum-up all the primary and relevant metabolic information that one needs to review to understand the complex and diverse role of the liver in metabolism. With the current epidemic of metabolic diseases, it is of immediate importance to understand the contribution of the liver in health and its role in the development of impaired metabolic regulation. Many studies have unmasked important roles that proteins expressed in the liver play in the development of or protection from metabolic diseases. Obesity is currently a worldwide public health burden that increases the risk for developing insulin resistance and several metabolic diseases such as diabetes, cardiovascular disease, inflammation and non-alcoholic fatty liver disease. Dietary approaches to limit fat intake are commonly prescribed to achieve the hypocaloric conditions necessary for weight loss. But dietary fat restriction is often accompanied by increased carbohydrate intake, which can dramatically increase endogenous fatty acid synthesis depending upon carbohydrate composition. It should be pointed out that although western societies consume high fat diets, the consumption of high carbohydrate diets in developing countries is on the rise. Since both dietary and endogenously synthesized fatty acids contribute to the whole-body fatty acid pool, obesity can therefore result from excessive fat or carbohydrate consumption. One of the major metabolic functions of the liver is to carry out de novo lipogenesis, which is the metabolic pathway that allows the conversion of excess carbohydrates into fatty acids. The process of de novo lipogenesis utilizes several enzymes that convert the two-carbon acetyl-coa into 16- and 18-carbon long chain saturated fatty acids (palmitate and stearate, respectively). Stearoyl-CoA desaturase (SCD) enzymes catalyze the conversion of palmitate and stearate into the monounsaturated fatty acids palmitoleate and oleate, which upon esterification into triglycerides are transported by very low-density lipoprotein (VLDL) to white adipose tissue (WAT) v
6 vi Preface for storage. There is also extensive crosstalk between the liver and WAT via signaling factors such as adipokines, lipokines and hepatokines that are involved in regulation of metabolic homeostasis. There is a vast literature and ongoing research on liver function. Our contributions in this book are focused on some aspects of metabolism. I am therefore extremely grateful to many people who have helped me make possible the current series on the role of the liver in de novo lipogenesis and metabolism. I would like to express my sincere appreciation to all contributors of the diverse chapters for their cooperation and excellent work. Without their participation this edition would not have been possible. I would like to thank Cori Praska, Mackenzie Carlson, and Andrew Denu who have helped in the editing of some chapters of the book. I would also like to thank Springer for their assistance and support during the course of this project. Finally I would like to thank my family for their support, encouragement and patience over the years. Madison, WI, USA James M. Ntambi, PhD
7 Contents 1 Transcriptional Regulation of De Novo Lipogenesis in Liver... 1 Deqiang Zhang and Lei Yin 2 The Molecular Basis of Hepatic De Novo Lipogenesis in Insulin Resistance Mengwei Zang 3 Regulation of Hepatic Metabolism by the Mechanistic Target of Rapamycin Dudley W. Lamming 4 FoxO1: A Conductor of Insulin Signaling to Glucose and Lipid Metabolism Ting Zhang and H. Henry Dong 5 Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease Sophie C. Cazanave and Arun J. Sanyal 6 Role of the Endocannabinoid System in Hepatic Lipogenesis Joseph Tam 7 Role of Lipogenesis and Lipid Desaturases in Non-alcoholic Fatty Liver Disease Mohamed Amine Lounis, Sabri Rial, James M. Ntambi, and Catherine Mounier 8 Lipid Droplet Proteins and Hepatic Lipid Metabolism Yumi Imai, Michelle B. Trevino, and Rexford S. Ahima 9 Influence of Gut Microbiota on Hepatic Lipogenesis and Disease Pathogenesis Vishal Singh, Beng San Yeoh, James M. Ntambi, and Matam Vijay-Kumar vii
8 viii Contents 10 Hepatic Lipogenesis: Nutritional Control and Pathophysiological Relevance Shih-Lung Woo, Ting Guo, and Chaodong Wu 11 Metabolic Rhythm of Hepatic Lipogenesis: Regulation and Roles in Metabolism David Jacobi, Hyunjii J. Cho, Ryan K. Alexander, and Chih-Hao Lee 12 Monounsaturated Fatty Acid Mediated Liver-Adipose Tissue Crosstalk and Metabolic Regulation Maggie S. Burhans and James M. Ntambi 13 Adipose Tissue DNL and Its Role in Metabolic Homeostasis Ludger Scheja and Christoph Buettner 14 The Lipogenic Effect of Insulin Revisited Sonia M. Najjar Index
9 Contributors Rexford S. Ahima, M.D., Ph.D. Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Ryan K. Alexander Division of Biological Sciences, Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA Christoph Buettner Department of Medicine and Department of Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA Maggie S. Burhans Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA Sophie C. Cazanave, Ph.D. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA Hyunjii J. Cho Division of Biological Sciences, Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA H. Henry Dong, Ph.D. Division of Pediatric Endocrinology, Department of Pediatrics, Childern s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Ting Guo Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA Yumi Imai, M.D. Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA David Jacobi Division of Biological Sciences, Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA ix
10 x Contributors Dudley W. Lamming Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison and William S. Middleton Memorial Veterans Hospital, Madison, WI, USA Chih-Hao Lee Division of Biological Sciences, Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA Mohamed Amine Lounis Département des Sciences Biologiques, Centre de recherche BioMed, Université du Québec à Montréal, Montréal, QC, Canada Catherine Mounier Département des Sciences Biologiques, Centre de recherche BioMed, Université du Québec à Montréal, Montréal, QC, Canada Sonia M. Najjar, Ph.D. Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA James M. Ntambi Department of Biochemistry, University of Wisconsin- Madison, Madison, WI, USA Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA Sabri Rial Département des Sciences Biologiques, Centre de recherche BioMed, Université du Québec à Montréal, Montréal, QC, Canada Arun J. Sanyal, M.D. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA Ludger Scheja Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Vishal Singh Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA Joseph Tam Obesity and Metabolism Laboratory, Faculty of Medicine, The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel Michelle B. Trevino Department of Internal Medicine, The Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA Matam Vijay-Kumar, Ph.D. Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA Shih-Lung Woo Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA
11 Contributors xi Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA Beng San Yeoh Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA Lei Yin, Ph.D. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA Mengwei Zang, M.D., Ph.D. Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA Deqiang Zhang, Ph.D. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA Ting Zhang Division of Pediatric Endocrinology, Department of Pediatrics, Childern s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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