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Semin Liver Dis 2023; 43(01): 077-088
DOI: 10.1055/s-0043-1762585
Review Article

Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration

Taylor J. Kelty
1   Department of Biomedical Sciences, University of Missouri - Columbia, Columbia, Missouri
2   Department of Nutrition and Exercise Physiology, University of Missouri - Columbia, Columbia, Missouri
3   NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri
,
Ryan J. Dashek
1   Department of Biomedical Sciences, University of Missouri - Columbia, Columbia, Missouri
3   NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri
4   Comparative Medicine Program, University of Missouri - Columbia, Columbia, Missouri
,
W. David Arnold
3   NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri
5   Physical Medicine and Rehabilitation, University of Missouri - Columbia, Columbia, Missouri
,
R. Scott Rector
2   Department of Nutrition and Exercise Physiology, University of Missouri - Columbia, Columbia, Missouri
3   NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri
6   Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri
7   Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri - Columbia, Columbia, Missouri
› Author Affiliations Funding This study received funding from the U.S. Department of Health and Human Services, National Institutes of Health: R01 AG070928, R01 DK113701, R01 DK130243, R01 DK130340.
› Further Information
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Abstract

The association between liver and brain health has gained attention as biomarkers of liver function have been revealed to predict neurodegeneration. The liver is a central regulator in metabolic homeostasis. However, in nonalcoholic fatty liver disease (NAFLD), homeostasis is disrupted which can result in extrahepatic organ pathologies. Emerging literature provides insight into the mechanisms behind the liver–brain health axis. These include the increased production of liver-derived factors that promote insulin resistance and loss of neuroprotective factors under conditions of NAFLD that increase insulin resistance in the central nervous system. In addition, elevated proinflammatory cytokines linked to NAFLD negatively impact the blood–brain barrier and increase neuroinflammation. Furthermore, exacerbated dyslipidemia associated with NAFLD and hepatic dysfunction can promote altered brain bioenergetics and oxidative stress. In this review, we summarize the current knowledge of the crosstalk between liver and brain as it relates to the pathophysiology between NAFLD and neurodegeneration, with an emphasis on Alzheimer's disease. We also highlight knowledge gaps and future areas for investigation to strengthen the potential link between NAFLD and neurodegeneration.

Keywords

nonalcoholic fatty liver disease - neurodegeneration - inflammation - insulin - mitochondria


Publication History

Article published online:
10 February 2023

© 2023. Thieme. All rights reserved.

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