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The role of omics in the pathophysiology, diagnosis and treatment of non-alcoholic fatty liver disease

Authors :
Nikolaos Perakakis
Konstantinos Stefanakis
Christos S. Mantzoros
Source :
Metabolism
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose spectrum covers clinical, histological and pathophysiological developments ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver fibrosis, potentially evolving into cirrhosis, hepatocellular carcinoma and liver failure. Liver biopsy remains the gold standard for diagnosing NAFLD, while there are no specific treatments. An ever-increasing number of high-throughput Omics investigations on the molecular pathobiology of NAFLD at the cellular, tissue and system levels produce comprehensive biochemical patient snapshots. In the clinical setting, these applications are considerably enhancing our efforts toward obtaining a holistic insight on NAFLD pathophysiology. Omics are also generating non-invasive diagnostic modalities for the distinct stages of NAFLD, that remain though to be validated in multiple, large, heterogenous and independent cohorts, both cross-sectionally as well as prospectively. Finally, they aid in developing novel therapies. By tracing the flow of information from genomics to epigenomics, transcriptomics, proteomics, metabolomics, lipidomics and glycomics, the chief contributions of these techniques in understanding, diagnosing and treating NAFLD are summarized herein.<br />Highlights • Numerous non-invasive NAFLD biomarkers are developed but none is broadly applicable • OMICS enrich the understanding, diagnosis and treatment of NAFLD, NASH and fibrosis • Genomics and epigenomics pinpoint NAFLD polymorphisms and DNA methylation loci • Transcriptomics and proteomics prove the diagnostic value of miRNAs and peptides • Metabolomics, lipidomics and glycomics offer robust panels and therapeutic insight

Subjects

Subjects :
Proteomics
HCC, Hepatocellular carcinoma
Cirrhosis
SWE, Shear wave elastography
Endocrinology, Diabetes and Metabolism
TM6SF2, Transmembrane 6 superfamily member 2
Disease
CK-18, Cytokeratin-18
GCKR, Glucokinase regulatory protein
HDACis, HDAC inhibitors
transcriptomics
HSI, Hepatic Steatosis index
0302 clinical medicine
Endocrinology
DAG, Diacylglycerol
EPA, Eicosapentanoic acid
MRI-PDFF, Magnetic resonance imaging derived proton density fat fraction
PE, Phosphatidylethanolamine
lncRNA, Long noncoding RNA
CAP, Controlled attenuation parameter
IgG, Immunoglobulin G
NASH
NAFLD, Non-alcoholic fatty liver disease
Genomics
TGF, Transforming growth factor
DHA, Docosahexaenoic acid
GRS, Genetic risk score
CRP, C-reactive protein
DHEA, Dehydroepiandrosterone
DNMTis, DNA methylation inhibitors
medicine.medical_specialty
PDGF, Platelet-derived growth factor
NASH, non-alcoholic steatohepatitis
DZNep, 3-deazaneplanocin A
tRNA, Transport RNA
PLA2, Phospholipase A2
digestive system
Article
TG, Triglyceride
03 medical and health sciences
IL-32, Interleukin 32
AUROC, Area under the receiver operator characteristics
Humans
Metabolomics
MS, Mass Spectrometry
SPM, Specialized pro-resolving mediator
nutritional and metabolic diseases
TOF, Time-of-flight
medicine.disease
Omics
AST, Aspartate transaminase
PNPLA3, Patatin-like phospholipase domain-containing-3
digestive system diseases
NAFL, Non-alcoholic fatty liver
030104 developmental biology
FXR, Farnesoid X receptor
PTPRE, protein-tyrosine phosphatase epsilon
Steatohepatitis
IGF, Insulin growth factor
ROS, Reactive oxygen species
ACC, Acetyl-coA carboxylase
Liver Cirrhosis
0301 basic medicine
F#, Fibrosis (score)
LPE, Lysophosphatidylethanolamine
LSM, Liver stiffness measurement
IL-32, Interleukin-32
VCTE, Vibration-controlled transient elastography
Bioinformatics
glycomics
HAT, Histone acetyltransferase
Non-alcoholic Fatty Liver Disease
APRI, Aspartate aminotransferase to platelet ratio index
steatosis
FADS, Fatty acid desaturase
circRNA, Circular RNA
NFS, NAFLD fibrosis score
PUFA, Polyunsaturated fatty acid
SNP, Single nucleotide polymorphism
NAS, NAFLD activity score
medicine.diagnostic_test
Fatty liver
AA, Arachidonic acid
IL-10, Interleukin-10
SFA, Saturated fatty acids
Liver biopsy
LPC, Lysophosphatidylcholine
FIB-4, Fibrosis-4 score
IGFBP, Insulin growth factor binding protein
ApoE, Apolipoprotein E
GGT, Gamma-glutamyltransferase
ChREBP, Carbohydrate
responsive element-binding protein
MUFA, Monounsaturated fatty acid
PC, Phosphatidylcholine
030209 endocrinology & metabolism
PPAR, Peroxisome proliferator-activated receptor
HFD, High fat diet
Internal medicine
medicine
Animals
MetS, Metabolic syndrome
IL-6, Interleukin-6
MRE, magnetic resonance elastography
SIRT, Sirtuin
SELDI, Surface-enhanced laser desorption/ionization
BMI, Body mas index
business.industry
HDAC, Histone deacetylase
WC, Waist circumference
ALT, Alanine aminotransferase
CHI3L1, Chitinase 3 Like 1
FFA, Free fatty acids
GWAS, Genome - wide association studies
epigenomics
HSD17B13, 17-b retinol dehydrogenase 13
miR, Micro RNA
lipidomics
1H-MRS, Magnetic resonance imaging and proton spectroscopy
MBOAT7, Membrane bound O-acyltransferase domain-containing 7
Steatosis
business
OR, Odds ratio
T2DM, Type 2 Diabetes Mellitus

Details

ISSN :
00260495
Volume :
111
Database :
OpenAIRE
Journal :
Metabolism
Accession number :
edsair.doi.dedup.....29bb96bcd7fb056ebf01eec2214ad114
Full Text :
https://doi.org/10.1016/j.metabol.2020.154320