TY - JOUR
T1 - Oxidative Stress in Non-Alcoholic Fatty Liver Disease
AU - SMIRNE, Carlo
AU - Croce, Eleonora
AU - Benedetto, Davide Di
AU - CANTALUPPI, Vincenzo
AU - COMI, Cristoforo
AU - SAINAGHI, Pier Paolo
AU - Minisini, Rosalba
AU - GROSSINI, Elena
AU - PIRISI, Mario
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022
Y1 - 2022
N2 - Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple
factors, which may partly explain why it still remains an orphan of adequate therapies. This review
highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive
oxygen species generators, including those produced in the gastrointestinal tract, contribute to
the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically
active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis
and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect
also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and
endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the
physiological antioxidant response. Therefore, modulation of this defense system emerges as an
interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics,
diet, and fecal microbiota transplantation represent new therapeutic approaches targeting
the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual
genetic and epigenetic factors as well. In the near future, precision medicine taking into
consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers,
will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further
personalizing treatments.
AB - Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple
factors, which may partly explain why it still remains an orphan of adequate therapies. This review
highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive
oxygen species generators, including those produced in the gastrointestinal tract, contribute to
the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically
active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis
and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect
also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and
endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the
physiological antioxidant response. Therefore, modulation of this defense system emerges as an
interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics,
diet, and fecal microbiota transplantation represent new therapeutic approaches targeting
the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual
genetic and epigenetic factors as well. In the near future, precision medicine taking into
consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers,
will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further
personalizing treatments.
KW - antioxidants
KW - gut microbiota
KW - inflammation
KW - lipid metabolism
KW - lipotoxicity
KW - metabolic syndrome
KW - mitochondrial dysfunction
KW - non-alcoholic fatty liver disease
KW - oxidative stress
KW - reactive
oxygen species
KW - antioxidants
KW - gut microbiota
KW - inflammation
KW - lipid metabolism
KW - lipotoxicity
KW - metabolic syndrome
KW - mitochondrial dysfunction
KW - non-alcoholic fatty liver disease
KW - oxidative stress
KW - reactive
oxygen species
UR - https://iris.uniupo.it/handle/11579/133433
U2 - 10.3390/livers2010003
DO - 10.3390/livers2010003
M3 - Article
SN - 2673-4389
VL - 2
SP - 30
EP - 76
JO - LIVERS
JF - LIVERS
IS - 1
ER -