TY - JOUR
T1 - Non-alcoholic Fatty Liver Disease
T2 - Also a Disease of the Brain? A Systematic Review of the Preclinical Evidence
AU - Mikkelsen, Anne Catrine Daugaard
AU - Kjærgaard, Kristoffer
AU - Mookerjee, Rajeshwar Prosad
AU - Vilstrup, Hendrik V Arenstorff
AU - Wegener, Gregers
AU - Bay-Richter, Cecilie
AU - Thomsen, Karen Louise
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2024/6
Y1 - 2024/6
N2 - Non-alcoholic fatty liver disease (NAFLD) currently affects 25% of the global adult population. Cognitive impairment is a recently recognised comorbidity impeding memory, attention, and concentration, affecting the patients' activities of daily living and reducing their quality of life. This systematic review provides an overview of the evidence for, and potential pathophysiological mechanisms behind brain dysfunction at a neurobiological level, in preclinical NAFLD. We performed a systematic literature search for animal models of NAFLD studying intracerebral conditions using PubMed, Embase and Scopus. We included studies that reported data on neurobiology in rodent and pig models with evidence of steatosis or steatohepatitis assessed by liver histology. 534 unique studies were identified, and 30 studies met the selection criteria, and were included. Findings of neurobiological changes were divided into five key areas: (1) neuroinflammation, (2) neurodegeneration, (3) neurotransmitter alterations, (4) oxidative stress, and (5) changes in proteins and synaptic density. Despite significant heterogeneity in the study designs, all but one study of preclinical NAFLD reported changes in one or more of the above key areas when compared to control animals. In conclusion, this systematic review supports an association between all stages of NAFLD (from simple steatosis to non-alcoholic steatohepatitis (NASH)) and neurobiological changes in preclinical models.
AB - Non-alcoholic fatty liver disease (NAFLD) currently affects 25% of the global adult population. Cognitive impairment is a recently recognised comorbidity impeding memory, attention, and concentration, affecting the patients' activities of daily living and reducing their quality of life. This systematic review provides an overview of the evidence for, and potential pathophysiological mechanisms behind brain dysfunction at a neurobiological level, in preclinical NAFLD. We performed a systematic literature search for animal models of NAFLD studying intracerebral conditions using PubMed, Embase and Scopus. We included studies that reported data on neurobiology in rodent and pig models with evidence of steatosis or steatohepatitis assessed by liver histology. 534 unique studies were identified, and 30 studies met the selection criteria, and were included. Findings of neurobiological changes were divided into five key areas: (1) neuroinflammation, (2) neurodegeneration, (3) neurotransmitter alterations, (4) oxidative stress, and (5) changes in proteins and synaptic density. Despite significant heterogeneity in the study designs, all but one study of preclinical NAFLD reported changes in one or more of the above key areas when compared to control animals. In conclusion, this systematic review supports an association between all stages of NAFLD (from simple steatosis to non-alcoholic steatohepatitis (NASH)) and neurobiological changes in preclinical models.
KW - Neurodegeneration
KW - Neuroinflammation
KW - Neurotransmitters
KW - Non-alcoholic fatty liver disease
KW - Oxidative stress
KW - Synaptic density
U2 - 10.1007/s11064-022-03551-x
DO - 10.1007/s11064-022-03551-x
M3 - Review
C2 - 35230646
SN - 0364-3190
VL - 49
SP - 1468
EP - 1488
JO - Neurochemical Research
JF - Neurochemical Research
IS - 6
ER -