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Metabolism and Metabolomics of Liver in Health and Disease Metabolism and Metabolomics of Liver in Health and Disease • Walter Wahli and Hervé Guillou Metabolism and Metabolomics of Liver in Health and Disease Edited by Walter Wahli and Hervé Guillou Printed Edition of the Special Issue Published in Metabolites www.mdpi.com/journal/metabolites Metabolism and Metabolomics of Liver in Health and Disease Metabolism and Metabolomics of Liver in Health and Disease Editors Walter Wahli Herv´eGuillou MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editors Walter Wahli Herv´e Guillou University of Lausanne INRA ToxAlim Switzerland France Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Coatings (ISSN 2079-6412) (available at: https://www.mdpi.com/journal/metabolites/special issues/liver). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03943-635-4 (Hbk) ISBN 978-3-03943-636-1 (PDF) © 2021 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editors .............................................. vii Preface to ”Metabolism and Metabolomics of Liver in Health and Disease” ........... ix Lorraine Smith, Joran Villaret-Cazadamont, Sandrine P. Claus, C´ecileCanlet, Herv´e Guillou, Nicolas J. Cabaton and Sandrine Ellero-Simatos Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions Reprinted from: Metabolites 2020, 10, 104, doi:10.3390/metabo10030104 ............... 1 Aur´elien Amiel, Marie Tremblay-Franco, Roselyne Gautier, Simon Ducheix, Alexandra Montagner, Arnaud Polizzi, Laurent Debrauwer, Herve´ Guillou, Justine Bertrand-Michel and C´ecile Canlet Proton NMR Enables the Absolute Quantification of Aqueous Metabolites and Lipid Classes in Unique Mouse Liver Samples Reprinted from: Metabolites 2020, 10, 9, doi:10.3390/metabo10010009 ................ 19 Matthias Cuykx, Charlie Beirnaert, Robim Marcelino Rodrigues, Kris Laukens, Tamara Vanhaecke and Adrian Covaci Exposure of HepaRG Cells to Sodium Saccharin Underpins the Importance of Including Non-Hepatotoxic Compounds When Investigating Toxicological Modes of Action Using Metabolomics Reprinted from: Metabolites 2019, 9, 265, doi:10.3390/metabo9110265 ................ 39 Vivaldy Prinville, Leanne Ohlund and Lekha Sleno Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS Reprinted from: Metabolites 2020, 10, 26, doi:10.3390/metabo10010026 ................ 49 Ana Margarida Ara ujo,´ Maria Enea, F´elix Carvalho, Maria de Lourdes Bastos, M´arcia Carvalho and Paula Guedes de Pinho Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study Reprinted from: Metabolites 2019, 9, 228, doi:10.3390/metabo9100228 ................ 61 Fabienne Rajas, Amandine Gautier-Stein and Gilles Mithieux Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism Reprinted from: Metabolites 2019, 9, 282, doi:10.3390/metabo9120282 ................ 75 Sandra Steensels, Jixuan Qiao and Baran A. Ersoy Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease Reprinted from: Metabolites 2020, 10, 283, doi:10.3390/metabo10070283 ............... 89 George N. Ioannou, G. A. Nagana Gowda, Danijel Djukovic and Daniel Raftery Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach Reprinted from: Metabolites 2020, 10, 168, doi:10.3390/metabo10040168 ...............123 Maria Guarino and Jean-Fran¸coisDufour Nicotinamide and NAFLD: Is There Nothing New Under the Sun? Reprinted from: Metabolites 2019, 9, 180, doi:10.3390/metabo9090180 ................139 v Manuel Garc´ıa-Jaramillo, Kelli A. Lytle, Melinda H. Spooner and Donald B. Jump A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice Reprinted from: Metabolites 2019, 9, 252, doi:10.3390/metabo9110252 ................157 Xiangjin Meng, Xin Guo, Jing Zhang, Junji Moriya, Junji Kobayashi, Reimon Yamaguchi and Sohsuke Yamada Acupuncture on ST36, CV4 and KI1 Suppresses the Progression of Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease in Mice Reprinted from: Metabolites 2019, 9, 299, doi:10.3390/metabo9120299 ................181 Diren Beyo˘glu and Jeffrey R. Idle Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy Reprinted from: Metabolites 2020, 10, 50, doi:10.3390/metabo10020050 ................197 vi About the Editors Walter Wahli is a Professor emeritus at the Center for Integrative Genomics, University of Lausanne, Switzerland and Visiting Professor of Metabolic Disease at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Until recently, he was also the President of the Council of the Nestle Foundation for the Study of Problems of Nutrition in the World. He is internationally recognized as a leader in the field of molecular endocrinology and metabolism and discovered the nuclear hormone receptors peroxisome proliferator-activated receptors β and γ (PPARβ and PPARγ ). He has received several awards for the elucidation of key functions of these receptors, which are activated by fatty acids and fatty acid derivatives. Synthetic PPAR agonists are drugs used mainly for lowering triglycerides and blood sugar. Prior to his present appointments, Walter Wahli was a visiting associate at the National Cancer Institute, National Institutes of Health, Bethesda, USA. He then became a Professor and Director of the Institute of Animal Biology at the University of Lausanne. He was the Vice-Rector for Research and Continuing Education of the university and founded the Center of Integrative Genomics, which he directed for several years. He was also a member of the Swiss National Science Foundation Research Council and presided over the Biology and Medicine Division. Herv´e Guillou was trained in molecular biology and lipid biochemistry during his Ph.D. at Agrocampus Rennes. He was then a post-doctoral fellow in the Len Stephens and Phill Hawkins lab at the Babraham Institute working in the field of signaling by phosphatidylinositols in neutrophils. He was then recruited as a junior investigator and became a group leader in INRA Toulouse where he started to investigate the transcriptional control of liver physiology by nuclear receptors. vii Preface to ”Metabolism and Metabolomics of Liver in Health and Disease” The liver is a key organ, which has a multitude of functions. In fact, it is thought to be in charge of more than 500 processes ranging from protein synthesis, carbohydrate and lipid metabolism, detoxification of various natural and synthetic compounds, to the production of molecules promoting whole-body homeostasis, to name but a few. Most of these functions are carried out by hepatocytes. In line with its multitasking physiology, the liver consumes plenty of oxygen, up to about 20% of resting total body consumption, half of which is provided by the hepatic portal vein, while the other half is met by the hepatic arteries. The liver plays an essential role in the breaking down of nutrients, such as carbohydrates, lipids, and proteins derived from feeding on plants and animals to convert them to substances that are essential to the body. Furthermore, it is key in catabolizing or modifying toxic substances such as nicotine, alcohol, toxins, and drugs and environmental xenobiotics in a process called detoxication. The liver also plays an important role in the immune system. Finally, the regeneration capacity of the liver is astonishing. More than half of the liver can be removed and it will rapidly go back to normal size. Such a complex organ can be affected by many types of dysregulations causing diseases. Liver diseases represent a major global health problem in developed and developing countries. Most deaths are due to two conditions: hepatitis B infection and non-alcoholic fatty liver disease (NAFLD). Following an acute infection, hepatitis B becomes chronic in 5–20% of adults and causes severe health problems. NAFLD, which is quite common all over the globe is characterized by too much fat in the liver, which is often caused by lifestyle mainly overnutrition and insufficient physical activity. In adults, NAFLD is often associated with diabetes and obesity. Importantly, due to the progression of childhood obesity and children presenting increased vulnerability to genetic and environmental factors, NAFLD currently affects up to 20% of the pediatric population. The pathogenesis of NAFLD is very complex and plenty of hepatic mechanisms are implicated, such as alterations in glucose and lipid metabolism as well as insulin signaling. Furthermore, dysfunctional cross-talks between the liver and other organs, such as the adipose tissues and the gut and its microbiota also participate in NAFLD development. There is currently
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