Hepatic De Novo Lipogenesis and Regulation of Metabolism

309 Pages·2016·6.767 MB·English

by  James M Ntambi (eds.)

James M. Ntambi Editor
Hepatic
De Novo
Lipogenesis
and Regulation
of Metabolism
Hepatic De Novo Lipogenesis and Regulation
of Metabolism

James M. Ntambi
Editor
Hepatic De Novo Lipogenesis
and Regulation of Metabolism
Editor
James M. Ntambi
Department of Biochemistry
University of Wisconsin-Madison
Madison , WI , USA
ISBN 978-3-319-25063-2 ISBN 978-3-319-25065-6 (eBook)
DOI 10.1007/978-3-319-25065-6
Library of Congress Control Number: 2015956534
Springer Cham Heidelberg New York Dordrecht London
© Springer International Publishing Switzerland 2016
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Pref ace
T he 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 informa-
tion 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, car-
diovascular disease, infl ammation 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 accompa-
nied 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 lipogen-
esis, which is the metabolic pathway that allows the conversion of excess carbohy-
drates 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 esterifi cation into triglycerides are
transported by very low-density lipoprotein (VLDL) to white adipose tissue (WAT)
v
vi Preface
for storage. There is also extensive crosstalk between the liver and WAT via signal-
ing factors such as adipokines, lipokines and hepatokines that are involved in regu-
lation of metabolic homeostasis.
T here is a vast literature and ongoing research on liver function. Our contribu-
tions 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
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 ............................................................................... 33
Mengwei Zang
3 Regulation of Hepatic Metabolism by the Mechanistic
Target of Rapamycin............................................................................... 59
Dudley W. Lamming
4 FoxO1: A Conductor of Insulin Signaling to Glucose
and Lipid Metabolism............................................................................. 79
Ting Zhang and H. Henry Dong
5 Molecular Mechanisms of Lipotoxicity in Nonalcoholic
Fatty Liver Disease .................................................................................. 101
Sophie C. Cazanave and Arun J. Sanyal
6 Role of the Endocannabinoid System in Hepatic Lipogenesis ............ 131
Joseph Tam
7 Role of Lipogenesis and Lipid Desaturases in Non-alcoholic
Fatty Liver Disease .................................................................................. 143
Mohamed Amine Lounis , Sabri Rial , James M. Ntambi ,
and Catherine Mounier
8 Lipid Droplet Proteins and Hepatic Lipid Metabolism ....................... 165
Yumi Imai , Michelle B. Trevino , and Rexford S. Ahima
9 Influence of Gut Microbiota on Hepatic Lipogenesis
and Disease Pathogenesis ....................................................................... 189
Vishal Singh , Beng San Yeoh , James M. Ntambi ,
and Matam Vijay-Kumar
vii
viii Contents
10 Hepatic Lipogenesis: Nutritional Control
and Pathophysiological Relevance ......................................................... 211
Shih-Lung Woo , Ting Guo , and Chaodong Wu
11 Metabolic Rhythm of Hepatic Lipogenesis: Regulation
and Roles in Metabolism ........................................................................ 235
David Jacobi , Hyunjii J. Cho , Ryan K. Alexander ,
and Chih-Hao Lee
12 Monounsaturated Fatty Acid Mediated Liver- Adipose
Tissue Crosstalk and Metabolic Regulation ......................................... 255
Maggie S. Burhans and James M. Ntambi
13 Adipose Tissue DNL and Its Role in Metabolic Homeostasis ............. 267
Ludger Scheja and Christoph Buettner
14 The Lipogenic Effect of Insulin Revisited ............................................. 285
Sonia M. Najjar
Index ................................................................................................................. 297
Contributors
Rexford S. Ahima , M.D., Ph.D. Division of Endocrinology, Diabetes and
Metabolism, P erelman 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. D ivision of Gastroenterology, Hepatology and
Nutrition, Department of Internal Medicine, Virginia Commonwealth University,
Richmond, VA, USA
Hyunjii J. Cho D ivision 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, C hildern’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 D ivision of Biological Sciences, Department of Genetics and
Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
ix