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Carsten Carlberg · Stine Marie Ulven
Ferdinand Molnár

Nutrigenomics:
How Science
Works

[email protected]
Nutrigenomics: How Science Works
Carsten Carlberg • Stine Marie Ulven
Ferdinand Molnár

Nutrigenomics: How Science

Works
Carsten Carlberg Stine Marie Ulven
Institute of Biomedicine Department of Nutrition
University of Eastern Finland University of Oslo
Kuopio, Finland Oslo, Norway

Ferdinand Molnár
Department of Biology
Nazarbayev University
Nur-Sultan, Kazakhstan

ISBN 978-3-030-36947-7 ISBN 978-3-030-36948-4 (eBook)

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© Springer Nature Switzerland AG 2020

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the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
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Preface

Our daily diet is more than a collection of carbohydrates, lipids, and proteins, min-
erals, and vitamins that provide energy and serve as building blocks of our life. It is
also the most dominant environmental signal to which we are exposed from womb
to death. The availability of the sequence of the complete human genome and the
consequent development of next-generation sequencing technologies have signifi-
cantly affected nearly all areas of bioscience. This was the starting point for new
disciplines, such as genomics and its subdiscipline nutrigenomics. The fascinating
area of nutrigenomics describes the daily communication between dietary mol-
ecules, their metabolites, and our genome. Its genomic components comprise not
only the variation of the human genome, such as SNPs (single-nucleotide polymor-
phisms), but also the dynamic packaging of the genome into chromatin, including
all information stored in this epigenome. Moreover, this book discusses the proteins
that are involved in the signal transduction between dietary molecules and the
genome, such as nuclear receptors, chromatin-modifying enzymes, and energy
status-sensing kinases, and their mechanism of action.
Most noncommunicable diseases, such as T2D (type 2 diabetes) and CVDs (car-
diovascular diseases), are the basis of lifestyle decisions. They have not only a
genetic, inherited component, but to some 80%, they are based on epigenetics
(meaning “above” genetics), i.e., on our lifestyle choices and environmental expo-
sures, such as what we eat. We cannot change the genes that we are born with, but
we can take care of the rest being primarily based on our epigenome. This means
that the genetic predisposition for a disease can be counterbalanced by an appropri-
ate healthy lifestyle that modulates the epigenome of the affected tissues. It is well
known that there is a high level of individual responsibility for staying healthy, but
a detailed understanding of epigenetics provides a molecular explanation for this
life attitude. This book describes how nutrition shapes human evolution and demon-
strates its consequences for our susceptibility to diseases, such as T2D and athero-
sclerosis, the underlying cause of most CVDs. 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

v
vi Preface

life in the savannas of East Africa. Thus, this book does not only discuss about a
theoretical topic in science, but it especially talks about real life and our lifelong
“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 of how our key daily
lifestyle decision affects our health.
The purpose of this book is to provide an overview on the principles of nutrig-
enomics and their relation to health and 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 essen-
tials 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 the book is linked to a series of lecture courses in “Molecular
Medicine and Genetics,” “Molecular Immunology,” “Cancer Biology,” and
“Nutrigenomics” that are given by one of us (C. Carlberg) in different forms since
2002 at the University of Eastern Finland in Kuopio. This book represents an
updated version of our textbook Nutrigenomics (ISBN 978-3-319-30415-1).
However, we shortened and simplified the content in order to give also undergradu-
ate students and other people engaged in life sciences an easier start into the topic.
This book also relates to our textbooks Mechanisms of Gene Regulation (ISBN
978-94-017-7741-4), Human Epigenomics (ISBN 978-981-10-7614-8), and Human
Epigenetics: How Science Works (ISBN 978-3-030-22906-1), the studying of which
may be interesting to readers who like to get more detailed information. Following
two introductory chapters, the first five chapters of this book will explain the molec-
ular basis of nutrigenomics, while the last three chapters will provide examples for
the impact of nutrigenomics on our health and disease. A glossary in the appendix
will explain the major specialist’s terms.
We hope that the readers will enjoy this rather visual book and get as enthusiastic
about nutrigenomics as the authors are.

Kuopio, Finland Carsten Carlberg

Oslo, Norway Stine Marie Ulven
Nur-Sultan, Kazakhstan Ferdinand Molnár
October 2019
Acknowledgments

The authors would like to thank Eunike Velleuer, MD, and Andrea Hanel, BSc, for
extensive proofreading and constructive criticism.

vii
Contents

1 Nutrition and Common Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 Evolution of Human Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Principles of Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Dietary Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.4 Nutrition and Metabolic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.5 Nutrition and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.6 Impact of Physical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2 Human Genomic Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1 Migration and Evolutionary Challenges of Homo sapiens . . . . . . . 17
2.2 Diversity of Human Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.3 Genetic Variants of the Human Genome . . . . . . . . . . . . . . . . . . . . . 21
2.4 Haplotype Blocks and GWAS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.5 The 1000 Genomes Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3 Sensing Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.1 Nutrient-Sensing Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.2 Nuclear Receptors as Nutrient Sensors . . . . . . . . . . . . . . . . . . . . . . 35
3.3 Functions and Actions of PPARs . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.4 Integration of Lipid Metabolism by LXRs and FXR . . . . . . . . . . . . 41
3.5 Coordination of the Immune Response by VDR . . . . . . . . . . . . . . . 44
3.6 Circadian Control of Metabolic Processes. . . . . . . . . . . . . . . . . . . . 46
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
4 Interference of the Human Genome with Nutrients . . . . . . . . . . . . . . 49
4.1 Human Genetic Adaptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2 Genetic Adaption to Dietary Changes . . . . . . . . . . . . . . . . . . . . . . . 51
4.3 Regulatory SNPs and Quantitative Traits . . . . . . . . . . . . . . . . . . . . 53
4.4 Definition of Nutrigenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

ix
x Contents

4.5 Personal Omics Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5 Nutritional Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.1 Epigenetic Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
5.2 Intermediary Metabolism and Epigenetic Signaling . . . . . . . . . . . . 68
5.3 Nutrition-Triggered Transgenerational Epigenetic Inheritance . . . . 73
5.4 Population Epigenetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
6 Nutritional Signaling and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
6.1 Aging and Conserved Nutrient-Sensing Pathways . . . . . . . . . . . . . 81
6.2 Neuroendocrine Regulation of Aging . . . . . . . . . . . . . . . . . . . . . . . 84
6.3 Principles of Insulin Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
6.4 Central Role of FOXO Transcription Factors . . . . . . . . . . . . . . . . . 88
6.5 Calorie Restriction from Yeast to Mammals . . . . . . . . . . . . . . . . . . 91
6.6 Cellular Energy Status Sensing by Sirtuins and AMPK . . . . . . . . . 93
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
7 Chronic Inflammation and Metabolic Stress . . . . . . . . . . . . . . . . . . . . 99
7.1 The Central Role of Monocytes and Macrophages . . . . . . . . . . . . . 99
7.2 Acute and Chronic Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
7.3 Reverse Cholesterol Transport and Inflammation . . . . . . . . . . . . . . 107
7.4 Sensing Metabolic Stress via the ER . . . . . . . . . . . . . . . . . . . . . . . . 109
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
8 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
8.1 Definition of Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
8.2 Adipogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
8.3 Inflammation in Adipose Tissue. . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
8.4 Energy Homeostasis and Hormonal Regulation of Food Uptake . . 124
8.5 Genetics of Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
9 Insulin Resistance and Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
9.1 Glucose Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
9.2 Insulin Resistance in Skeletal Muscle and Liver . . . . . . . . . . . . . . . 135
9.3 β Cell Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
9.4 Definition of Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
9.5 Failure of Glucose Homeostasis in T2D and Its Treatment . . . . . . . 143
9.6 Genetics and Epigenetics of T2D. . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
10 Heart Disease and the Metabolic Syndrome. . . . . . . . . . . . . . . . . . . . . 153
10.1 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
10.2 Mechanisms of Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
10.3 Lipoproteins and Dyslipidemias . . . . . . . . . . . . . . . . . . . . . . . . . . 159
10.4 Whole body’s Perspective of the Metabolic Syndrome . . . . . . . . . 163
Contents xi

10.5 Metabolic Syndrome in Key Metabolic Organs. . . . . . . . . . . . . . . 167

10.6 Genetics and Epigenetics of the Metabolic Syndrome . . . . . . . . . 169
Additional Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
Abbreviations

1,25(OH)2D3 1,25-dihydroxyvitamin D3
25(OH)D3 25-hydroxyvitamin D3
3D 3-dimensional
α-MSH α-melanocyte-stimulating hormone
ABC ATP-binding cassette
ABL abetalipoproteinemia
AC adenylate cyclase
ACAT1 acetyl-CoA acetyltransferase 1
ACC acetyl-CoA carboxylase
ACL ATP citrate lyase
ADAMTS ADAM metallopeptidase with thrombospondin motif
ADH alcohol dehydrogenase
ADP adenosine diphosphate
ADRB3 adrenoceptor beta 3
AGRP agouti-related peptide
AKT AKT serine/threonine kinase
ALOX5 arachidonate 5-lipoxygenase
ALOX15 arachidonate 15-lipoxygenase
AMPK adenosine monophosphate-activated protein kinase
AMY amylase
ANGPTL2 angiopoietin-like protein 2
APEH N-acylaminoacyl-peptide hydrolase
AP1 activating protein 1
APO apolipoprotein
APPL1 adaptor protein, phosphotyrosine interacting with PH domain and
leucine zipper 1
AR androgen receptor
ARC arcuate nucleus
ARID AT-rich interaction domain
ARL4C ADP-ribosylation factor-like 4C
ARNTL aryl hydrocarbon receptor nuclear translocator-like

xiii
xiv Abbreviations

ASC apoptosis-associated speck

ASIP agouti-signaling protein
ATF6 activating transcription factor 6
ATP adenosine triphosphate
β-OHB β-hydroxybutyrate
BAAT bile acid-CoA:amino acid N-acetyltransferase
BAT brown adipose tissue
BDNF brain-derived neurotrophic factor
BLK B lymphoid tyrosine kinase
BMI body mass index
BMP bone morphogenetic protein
bp base pair
BRD bromodomain containing
CAMKK Ca2+/calmodulin-dependent protein kinase kinase
CAMP cathelicidin
CAR constitutive androstane receptor
CASP caspase
CBL Cbl proto-oncogene, E3 ubiquitin protein ligase
CCK cholecystokinin
CCL chemokine (C-C motif) ligand
CCR C-C chemokine receptor
CD36 CD36 molecule
CDC42 cell division cycle 42
CDKAL1 CDK5 regulatory subunit associated protein 1-like 1
CDKN cyclin-dependent kinase inhibitor
CDP common dendritic cell progenitor
CDX2 caudal type homeobox 2
CEBP CCAAT-binding protein
CEL carboxyl ester lipase
CETP cholesterol ester transfer protein
CETPD CETP deficiency
CHD coronary heart disease
CHGA chromogranin A
ChIP chromatin immunoprecipitation
CLOCK clock circadian regulator
CLP common lymphoid progenitor
CMP common myeloid progenitor
CNS central nervous system
CNV copy number variant
CPT1A carnitine palmitoyltransferase 1A
CREB3L3 cAMP responsive element binding protein 3-like 3
CREBBP CREB-binding protein, also called KAT3A
CRP C-reactive protein
CRTC2 CREB-regulated transcription coactivator 2
CRY1 cryptochrome circadian clock 1
Abbreviations xv

CSF2 colony-stimulating factor 2

CTNS cystinosin, lysosomal cystine transporter
CVD cardiovascular disease
CXCL5 chemokine (C-X-C motif) ligand 5
CXCR C-X-C motif chemokine receptor
CYP cytochrome P450
DAF abnormal dauer formation
DAG diacylglycerol
DALY disability-adjusted life year
DAMP damage-associated molecular pattern
DBL dysbetalipoproteinemia
DC dendritic cell
DCT dopachrome tautomerase
DEFB4 defensin, beta 4A
DNMT DNA methyltransferase
DOHaD Developmental Origins of Health and Disease
E% percent of total energy
EDAR ectodysplasin A receptor
EIF2A eukaryotic translation initiation factor 2A
EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3
EGIR European Group for the Study of Insulin Resistance
EHMT euchromatic histone-lysine N-methyltransferase
ENCODE Encyclopedia of DNA Elements
ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1
EP300 E1A binding protein p300, also called KAT3B
eQTL expression quantitative trait locus
ER endoplasmic reticulum
ERN1 endoplasmic reticulum to nucleus signaling 1
FABP6 ileal fatty acid binding protein
FAD flavin adenine dinucleotide
FANTOM functional annotation of the mammalian genome
FAS Fas cell surface death receptor
FASN fatty acid synthase
FCH familial combined hyperlipidemia
FFA free fatty acid
FGF fibroblast growth factor
FGFR4 FGF receptor 4
FH familial hypercholesterolemia
FHC familial hyperchylomicronemia
FHTG familial hypertriglyceridemia
FOXO forkhead box O
FTO fat mass and obesity-associated
FXR farnesoid X receptor
G6PC glucose-6-phosphatase
GAB1 GRB2-associated binder 1
xvi Abbreviations

GATA GATA binding protein

GCK glucokinase
GC gas chromatography
GH1 growth hormone 1
GIS1 GIg1-2 suppressor
GLP1 glucagon-like peptide 1
GMP granulocyte-monocyte progenitor
GPAT glycerol-3-phosphate acyltransferase
GPR G-protein-coupled receptor
GR glucocorticoid receptor
GRB growth factor receptor-bound protein
GSK3 glycogen synthase kinase 3
GSV GLUT4-containing storage vesicles
GWAS genome-wide association study
GYS glycogen synthase
HAT histone acetyltransferase
HBL hypobetalipoproteinemia
HDAC histone deacetylase
HDM histone demethylase
HDL high-density lipoprotein
HHEX hematopoietically expressed homeobox
HIF1 hypoxia-inducible factor 1
HIV human immunodeficiency virus
HLA human leukocyte antigen
HLD hepatic lipase deficiency
HLP hyperlipoproteinemia
HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase
HMT histone methyltransferase
HNF hepatocyte nuclear factor
HPT hypothalamic-pituitary-thyroid
HSC hematopoietic stem cell
HSF1 heat shock transcription factor 1
HSP heat shock protein
HTG hypertriglycerolemia
IAP intracisternal A particle
IDF International Diabetes Federation
IDH isocitrate dehydrogenase
IDOL inducible degrader of LDLR
IGF insulin-like growth factor
IGF1R IGF1 receptor
IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2
IKBK inhibitor of kappa light polypeptide gene enhancer in B cells, kinase
IL interleukin
IL1RN IL1 receptor antagonist
IMCL intramyocellular lipid
Abbreviations xvii

indel insertion-deletion
INFG interferon γ
INS insulin
iPOP integrative personal omics profiling
IR insulin receptor
IRE1 inositol-requiring enzyme
IRF interferon regulatory factor
IRS insulin receptor substrate
IRX iroquois homeobox
JAK Janus kinase
KATP ATP-sensitive K+
kb kilo base pairs (1000 bp)
KCNJ11 potassium inwardly rectifying channel, subfamily J, member 11
KCNQ1 potassium voltage-gated channel subfamily Q, member 1
KDM lysine demethylase
KLF Krüppel-like factor
KMT lysine methyltransferase
LCAT lecithin cholesterol acyltransferase
LCATD LCAT deficiency
LCR locus control region
LCT lactase
LDL low-density lipoprotein
LDLR LDL receptor
LDLRAP1 LDLR accessory protein 1
LEP leptin
LEPR leptin receptor
LINE long interspersed element
LIPC hepatic lipase
LIPE hormone-sensitive lipase
LIPG endothelial lipase
LPCAT3 lysophospholipid acyltransferase 3
LPL lipoprotein lipase
LRH-1 liver receptor homolog 1
LRP1 LDLR-related protein 1
LTR long terminal repeat
LXR liver X receptor
MAF minor allele frequency
MAFA v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog
A
MAN2A1 mannosidase, alpha, class 2A, member 1
MAPK mitogen-activated protein kinase
Mb mega base pairs (1,000,000 bp)
MC1R melanocortin 1 receptor
MC4R melanocortin 4 receptor
M-CFU myeloid stem cells
xviii Abbreviations

MCM6 minichromosome maintenance type 6

MDP macrophage and dendritic cell progenitor
MHC major histocompatibility complex
MHL mixed hyperlipidemia
mmHg millimeters of mercury
MODY maturity onset diabetes of the young
MPO myeloperoxidase
MPP multipotent progenitor
MS mass spectrometry
MSN multicopy suppressor of SNF1 mutation
MSR1 macrophage scavenger receptor 1
MTHFR methylenetetrahydrofolate reductase
MTNR1B melatonin receptor 1B
MTTP microsomal triglyceride transfer protein
MUFA monounsaturated
MYCL v-myc avian myelocytomatosis viral oncogene lung carcinoma
derived homolog
MYF5 myogenic factor 5
MYO5A myosin VA
NAD nicotinamide adenine dinucleotide
NAFLD nonalcoholic fatty liver disease
NAMPT nicotinamide mononucleotide phosphoribosyltransferase, also
called visfatin
NANOG nanog homeobox
NCOA nuclear receptor coactivator
NCEH1 neutral cholesterol ester hydrolase 1
NCEP National Cholesterol Education Program
ncRNA noncoding RNA
NEUROD1 neuronal differentiation 1
NEUROG3 neurogenin 3
NFκB nuclear factor κB
NLR NOD-like receptor
NLRP NLR protein
NO nitric oxide
NOS2 inducible nitric oxide synthase 2
NPC1L1 Niemann-Pick C1-like protein 1
NPY neuropeptide Y
NTS nucleus tractus solitarius
OCA2 OCA2 melanosomal transmembrane protein
OGTT oral glucose tolerance test
ORL1 oxidized low-density lipoprotein receptor 1
PAMP pathogen-associated molecular pattern
PAX paired box
PBMC peripheral blood mononuclear cell
PC pyruvate carboxylase
Abbreviations xix

PCK phosphoenolpyruvate carboxykinase

PCSK1 proprotein convertase subtilisin/kexin type 1
PDH pyruvate dehydrogenase
PDPK 3-phosphoinositide dependent protein kinase 1
PDX1 pancreatic and duodenal homeobox 1
PER1 period circadian clock 1
PFKFB2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2
PI3K phosphoinositide 3-kinase
PIP3 phosphatidylinositol-3,4,5-triphosphate
PKA protein kinase A
PLAU plasminogen activator, urokinase
PLTP phospholipid transfer protein
PNPLA patatin-like phospholipase domain-containing protein-3
Pol II RNA polymerase II
POMC proopiomelanocortin
POU1F1 POU class 1 homeobox 1
POU5F1 POU class 5 homeobox 1
PPAR peroxisome proliferator-activated receptor
PPARGC1A PPAR gamma, coactivator 1 alpha
PPP2 protein phosphatase 2
PRK protein kinase
PROP1 PROP paired-like homeobox 1
PRR pattern recognition receptor
PUFA polyunsaturated fatty acid
PTEN phosphatase and tensin homolog
PTGS2 prostaglandin-endoperoxide synthase 2 (also known as COX2)
PTPN1 protein tyrosine phosphatase, non-receptor type 1
PXR pregnane X receptor
RAPTOR regulatory-associated protein of TOR
RAR retinoic acid receptor
RBP4 retinol binding protein 4
RE response element
REV-ERB Reverse-Erb, official gene symbol NR1D1
RHOQ Ras homolog family, member Q
RIG1 retinoic acid-inducible gene 1
RLR RIG1-like helicase receptors
RNA-seq RNA sequencing
ROR RAR-related orphan receptor
ROS reactive oxygen species
RPS6K ribosomal protein S6 kinase
RXR retinoid X receptor
S6K S6 kinase
SAH S-adenosylhomocysteine
SAM S-adenosylmethionine
SCAP SREBF chaperone
xx Abbreviations

SCARB1 scavenger receptor class B member 1

SCD1 steroyl-CoA desaturase 1
SCN suprachiasmatic nucleus
SCNN1 sodium channel, non-voltage-gated 1
SERPINE1 serpin peptidase inhibitor, clade E (also called PAI-1)
SF-1 steroidogenic factor 1
SFA saturated fatty acids
SFRP5 frizzled-related protein 5
SH2 Src homology 2
SHC Src homology 2 domain-containing
SHP2 SH2-domain-containing tyrosine phosphatase 2
SI sucrase-isomaltase
SIM1 single-minded family bHLH transcription factor 1
SINE short interspersed element
SIRT sirtuin
SITO sitosterolemia
SLC solute carrier family
SLCO solute organic anion transporter
SNP single-nucleotide polymorphism
SNS sympathetic nervous system
SOCS suppressor of cytokine signaling
SORBS1 sorbin and SH3 domain-containing 1
SOS Son of Sevenless
SORT1 sortilin 1
SPI1 spleen focus-forming virus proviral integration oncogene, also
called PU.1
SREBF1 sterol regulatory element-binding transcription factor 1
STAT signal transducer and activator of transcription
SULT2A1 sulfotransferase family 2A, member 1
T1D type 1 diabetes
T2D type 2 diabetes
TAS1R2 taste receptor, type 1, member 2
TBC1D TBC1 domain family, member 1
TCA tricarboxylic acid
TCGA The Cancer Genome Atlas
TD Tangier disease
TET ten-eleven translocation
TGFB1 transforming growth factor beta 1
TH T helper
THRSP thyroid hormone responsive
TLR Toll-like receptor
TNF tumor necrosis factor
TNFR TNF receptor
TOR(C) target of rapamycin (complex)
TRAF2 TNF receptor-associated factor 2
 Abbreviations xxi

TREG regulatory T
TSC2 tuberous sclerosis 2
TSS transcription start site
TYR tyrosinase
UBR1 ubiquitin protein ligase E3 component n-recognin 1
UCP uncoupling protein
UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4
UNC5B unc-5 homolog B
UV ultraviolet
VDR vitamin D receptor
VLDL very low-density lipoprotein
VNN vanin 1
WAT white adipose tissue
WHO World Health Organization
WHR waist-hip ratio
WNT wingless-type MMTV integration site family member
YWHA tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activa-
tion protein (also called 14-3-3)
XBP1 X-box binding protein 1

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