Nutrigenomics

The fascinating area of Nutrigenomics describes this daily communication between diet, food and nutrients, their metabolites and our genome. This book describes how nutrition shapes human evolution and demonstrates its consequences for our susceptibility to diseases, such as diabetes and atherosclerosis. Inappropriate diet can yield stress for our cells, tissues and organs and then it is often associated with low-grade chronic inflammation. Overnutrition paired with physical inactivity leads to overweight and obesity and results in increased burden for a body that originally was adapted for a life in the savannas of East Africa. Therefore, this textbook does not discuss a theoretical topic in science, but it talks about real life, and our life-long “chat” with diet. We are all food consumers, thus each of us is concerned by the topic of this book and should be aware of its mechanisms. The purpose of this book is to provide an overview on the principles of nutrigenomics and their relation to health or disease. We are not aiming to compete with more comprehensive textbooks on molecular nutrition, evolutionary biology, genomics, gene regulation or metabolic diseases, but rather will focus on the essentials and will combine, in a compact form, elements from different disciplines. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule “a picture tells more than thousand words”. The content of this book is based on the lecture course “Nutrigenomics”, which is held since 2003 once per year by Prof. Carlberg at the University of Eastern Finland in Kuopio. The book is subdivided into three sections and twelve chapters. Following the "Introduction" there are sections on the "Molecular genetic basis" and the "Links to disease", which take a view on nutrigenomics from the perspective of molecular mechanisms or from the causes of metabolic diseases, respectively. Besides its value as a textbook, Nutrigenomics will be a usefull reference for individuals working in biomedicine. Preface 6 Acknowledgements 8 Contents 10 Abbreviations 14 Part I: Introduction 23 Chapter 1: Nutrition and Common Diseases 24 1.1 Human Nutrition 24 1.2 Nutrition and Obesity 29 1.3 Nutrition and Cancer 30 1.4 Nutrition and Diabetes 32 1.5 Nutrition and Cardiovascular Diseases 34 1.6 Impact of Exercise 41 Additional Reading 44 Chapter 2: Human Genomic Variation 45 2.1 Migration and Evolutionary Challenges of the Modern Human 46 2.2 Diversity of Human Populations 47 2.3 Genetic Variants of the Human Genome 50 2.4 The HapMap Project and Haplotype Blocks 53 2.5 Genome-wide Association Studies 55 2.6 Whole Genome Sequencing and the 1000 Genomes Project 60 Additional Reading 64 Part II: Molecular Genetic Basis 65 Chapter 3: Sensing Nutrition 66 3.1 Nutrient-Sensing Mechanisms 67 3.2 Nutrient Sensing via Nuclear Receptors 70 3.3 Functions and Actions of PPARs 75 3.4 Integration of Lipid Metabolism by LXRs and FXR 77 3.5 Coordination of the Immune Response by VDR 80 3.6 Circadian Control of Metabolic Processes 83 Additional Reading 88 Chapter 4: Adaption of the Human Genome to Dietary Changes 89 4.1 Definition of Nutrigenomics 90 4.2 Vitamin D and Skin Color 90 4.3 Human Genetic Adaption to Dietary Changes 94 4.4 Regulatory SNPs and Quantitative Traits 95 4.5 “Omics” Analysis in Nutrition Sciences 98 4.6 Integrative Personal Omics Profile 101 Additional Reading 104 Chapter 5: Nutritional Epigenomics 105 5.1 Epigenetics Mechanisms 106 5.2 Intermediary Metabolism and Epigenetic Signaling 109 5.3 One-Carbon Metabolism and DNA Methylation 112 5.4 Nutrition-Triggered Transgenerational Epigenetics in Mice 114 5.5 Epigenetic Programming in Humans 116 Additional Reading 122 Chapter 6: Nutritional Signaling and Aging 123 6.1 Aging and Conserved Nutrient-Sensing Pathways 124 6.2 Neuroendocrine Aging Regulation in Humans and Other Mammals 127 6.3 Calorie Restriction from Yeast to Mammals 128 6.4 Properties and Functions of Sirtuins 131 6.5 Cellular Energy Status Sensing by AMPK 135 Additional Reading 138 Chapter 7: Chronic Inflammation and Metabolic Stress 139 7.1 The Central Role of Monocytes and Macrophages 139 7.2 Acute and Chronic Inflammation 142 7.3 Reverse Cholesterol Transport and Inflammation 146 7.4 M1 and M2 Macrophages in Adipose Tissue 149 7.5 ER Stress Response 151 Additional Reading 155 Part III: Links to Diseases 156 Chapter 8: Obesity 157 8.1 Definition of Obesity 157 8.2 Adipogenesis 161 8.3 Energy Homeostasis 164 8.4 Hormonal Regulation of Food Anticipation 166 8.5 Adipose Tissue is an Endocrine Organ 168 8.6 Inflammation in Adipose Tissue 171 8.7 Genetics of Obesity 173 Additional Reading 177 Chapter 9: Glucose Homeostasis, Insulin Resistance and β Cell Failure 178 9.1 Glucose Homeostasis in Health 179 9.2 Principles of Insulin Signaling 182 9.3 Central Role of FOXO Transcription Factors 184 9.4 Insulin Resistance in Skeletal Muscle and Liver 188 9.5 β Cell Failure 191 Additional Reading 195 Chapter 10: Diabetes 196 10.1 Definition of Diabetes 196 10.2 Failure of Glucose Homeostasis in T2D and Its Treatment 200 10.3 Genetics of T2D 203 10.4 Thrifty Gene Hypothesis 206 Additional Reading 208 Chapter 11: Hypertension, Atherosclerosis and Dyslipidemias 210 11.1 Hypertension 210 11.2 Mechanisms of Atherosclerosis 212 11.3 Cholesterol Metabolism and Lipoproteins 217 11.4 Dyslipidemias 220 Additional Reading 223 Chapter 12: The Metabolic Syndrome 224 12.1 Definitions of the Metabolic Syndrome 224 12.2 Whole Body's Perspective on the Metabolic Syndrome 227 12.3 Metabolic Syndrome in Key Metabolic Organs 227 12.4 Genetic and Epigenetic Basis of the Metabolic Syndrome 232 Additional Reading 237 The fascinating area of Nutrigenomics describes this daily communication between diet, food and nutrients, their metabolites and our genome. This book describes how nutrition shapes human evolution and demonstrates its consequences for our susceptibility to diseases, such as diabetes and atherosclerosis. Inappropriate diet can yield stress for our cells, tissues and organs and then it is often associated with low-grade chronic inflammation. Overnutrition paired with physical inactivity leads to overweight and obesity and results in increased burden for a body that originally was adapted for a life in the savannas of East Africa. Therefore, this textbook does not discuss a theoretical topic in science, but it talks about real life, and our life-long ĺlchatĺl with diet. We are all food consumers, thus each of us is concerned by the topic of this book and should be aware of its mechanisms.^The purpose of this book is to provide an overview on the principles of nutrigenomics and their relation to health or disease. We are not aiming to compete with more comprehensive textbooks on molecular nutrition, evolutionary biology, genomics, gene regulation or metabolic diseases, but rather will focus on the essentials and will combine, in a compact form, elements from different disciplines. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule ĺla picture tells more than thousand wordsĺl. The content of this book is based on the lecture course ĺlNutrigenomicsĺl, which is held since 2003 once per year by Prof. Carlberg at the University of Eastern Finland in Kuopio. The book is subdivided into three sections and twelve chapters.^Following the "Introduction" there are sections on the "Molecular genetic basis" and the "Links to disease", which take a view on nutrigenomics from the perspective of molecular mechanisms or from the causes of metabolic diseases, respectively. Besides its value as a textbook, Nutrigenomics will be a usefull reference for individuals working in biomedicine The fascinating area of Nutrigenomics describes this daily communication between diet, food and nutrients, their metabolites and our genome. This book describes how nutrition shapes human evolution and demonstrates its consequences for our susceptibility to diseases, such as diabetes and atherosclerosis. Inappropriate diet can yield stress for our cells, tissues and organs and then it is often associated with low-grade chronic inflammation. Overnutrition paired with physical inactivity leads to overweight and obesity and results in increased burden for a body that originally was adapted for a life in the savannas of East Africa. Therefore, this textbook does not discuss a theoretical topic in science, but it talks about real life, and our life-long zchaty with diet. We are all food consumers, thus each of us is concerned by the topic of this book and should be aware of its mechanisms. The purpose of this book is to provide an overview on the principles of nutrigenomics and their relation to health or disease. We are not aiming to compete with more comprehensive textbooks on molecular nutrition, evolutionary biology, genomics, gene regulation or metabolic diseases, but rather will focus on the essentials and will combine, in a compact form, elements from different disciplines. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule za picture tells more than thousand wordsy. The content of this book is based on the lecture course zNutrigenomicsy, which is held since 2003 once per year by Prof. Carlberg at the University of Eastern Finland in Kuopio. The book is subdivided into three sections and twelve chapters. Following the "Introduction" there are sections on the "Molecular genetic basis" and the "Links to disease", which take a view on nutrigenomics from the perspective of molecular mechanisms or from the causes of metabolic diseases, respectively. Besides its value as a textbook, Nutrigenomics will be a usefull reference for individuals working in biomedicine Front Matter....Pages i-xxi Front Matter....Pages 1-1 Nutrition and Common Diseases....Pages 3-23 Human Genomic Variation....Pages 25-44 Front Matter....Pages 45-45 Sensing Nutrition....Pages 47-69 Adaption of the Human Genome to Dietary Changes....Pages 71-86 Nutritional Epigenomics....Pages 87-104 Nutritional Signaling and Aging....Pages 105-120 Chronic Inflammation and Metabolic Stress....Pages 121-137 Front Matter....Pages 139-139 Obesity....Pages 141-161 Glucose Homeostasis, Insulin Resistance and β Cell Failure....Pages 163-180 Diabetes....Pages 181-194 Hypertension, Atherosclerosis and Dyslipidemias....Pages 195-208 The Metabolic Syndrome....Pages 209-222