Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review
Abstract
:1. Introduction
2. Methods
3. NAFLD and MAFLD
4. Metabolic Syndrome and Insulin Resistance
5. The Microbiota
6. Oxidative Stress and Chronic Inflammation
7. Diet and Lifestyle
7.1. Mediterranean Diet
7.2. MD Mechanism: Antioxidant and Lipid Lowering Effects
7.3. Physical Activity
8. Genetics and Epigenetics
9. Endothelial Dysfunction
10. Clinical Impact
11. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
NAFLD | Non-alcoholic fatty liver disease |
MS | Metabolic syndrome |
IR | Insulin resistance |
CV | Cardiovascular |
HDL | High density lipoproteins |
FFAs | Free fatty acids |
ER | Endoplasmic reticulum |
PDFF | Proton density fat fraction |
MRI | Magnetic resonance imaging |
NASH | Non-alcoholic steatohepatitis |
HCC | Hepatocellular carcinoma |
T2DM | Type 2 diabetes mellitus |
BMI | Body Mass Index |
OGTT | Oral glucose tolerance test |
HbA1c | Glycated hemoglobin |
MAFLD | Metabolic associated fatty liver disease |
IRS | Insulin receptor |
PI3K | Phosphatidylinositol 3-kinase |
GLUT-4 | Glucose transporter protein type-4 |
TNF-α | Tumor necrosis factor-alpha |
SREBP-1/2 | Sterol regulatory element-binding protein-1/2 |
ChREBP | Carbohydrate-responsive element-binding protein |
PPAR-γ | Peroxisome proliferator-activated receptor gamma |
BA | Bile acids |
LPS | lipopolysaccharides |
SCFA | Short-chain fatty acids |
ROS | Reactive oxygen species |
O2•− | superoxidation radicals |
H2O2 | Hydrogen peroxide |
NADPH | Nicotinamide adenine dinucleotide phosphate hydrogen |
NF-κB | Nuclear factor kappa B |
JNK | Jun N-terminal kinase |
IKK | Inhibitor of nuclear factor kappa-B kinase |
EASL | European Association for the Study of Liver |
AASLD | American Association for the Study of Liver Disease |
PUFA | Polyunsaturated fatty acid |
MD | Mediterranean diet |
MUFA | Mono-unsaturated fatty acid |
IL | Interleukin |
LDL | Low density lipoprotein |
VLDL | Very low density lipoprotein |
SNPs | Single nucleotide polymorphisms |
PNPLA3 | Patatin like phospholipase domain-containing protein 3 |
HSC | Hepatic stellate cells |
LXR | Liver X receptor |
MBOAT-7 | Membrane Bound O-Acyltransferase Domain Containing 7 |
GCKR | glucokinase regulatory protein |
TGF-1 | Transforming growth factor beta 1 |
PDGF | Platelet-derived growth factor |
HAT | Histone acetyltransferase |
HDAC | Histone deacetylases |
SIRT | Sirtuins |
SFAs | Saturated fatty acids |
EDHF | hyperpolarizing factor of endothelial derivation |
ED | endothelial dysfunction |
NOS | Nitric oxide synthetase |
ESM-1 | Endocan |
HMGB1 | High mobility group box 1 protein |
CAD | coronary artery disease |
HCV | hepatitis C virus |
HBV | hepatitis B virus |
US | ultrasound |
CAP | Control attenuation parameter |
IMT | Intima-media thickness |
CKD | Chronic kidney disease |
PIP3 | Phosphatidylinositol (3,4,5)-trisphosphate |
aPKC | activated protein kinase C |
AKT1 | Protein kinase B |
GSK3 | Glycogen synthase kinase 3 |
mTOR | Mammalian target of rapamycin |
FOXO1 | Forkhead box protein O1 |
PDK1 | 3-Phosphoinositide-dependent protein kinase 1 |
P | phosphorylated |
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Rinaldi, L.; Pafundi, P.C.; Galiero, R.; Caturano, A.; Morone, M.V.; Silvestri, C.; Giordano, M.; Salvatore, T.; Sasso, F.C. Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review. Antioxidants 2021, 10, 270. https://doi.org/10.3390/antiox10020270
Rinaldi L, Pafundi PC, Galiero R, Caturano A, Morone MV, Silvestri C, Giordano M, Salvatore T, Sasso FC. Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review. Antioxidants. 2021; 10(2):270. https://doi.org/10.3390/antiox10020270
Chicago/Turabian StyleRinaldi, Luca, Pia Clara Pafundi, Raffaele Galiero, Alfredo Caturano, Maria Vittoria Morone, Chiara Silvestri, Mauro Giordano, Teresa Salvatore, and Ferdinando Carlo Sasso. 2021. "Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review" Antioxidants 10, no. 2: 270. https://doi.org/10.3390/antiox10020270