Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration

Taylor J. Kelty; Ryan J. Dashek; W. David Arnold; R. Scott Rector

doi:10.1055/s-0043-1762585

Seminars in Liver Disease, Table of Contents

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

¹Department of Biomedical Sciences, University of Missouri - Columbia, Columbia, Missouri

²Department of Nutrition and Exercise Physiology, University of Missouri - Columbia, Columbia, Missouri

³NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri

,

Ryan J. Dashek

¹Department of Biomedical Sciences, University of Missouri - Columbia, Columbia, Missouri

³NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri

⁴Comparative Medicine Program, University of Missouri - Columbia, Columbia, Missouri

,

W. David Arnold

³NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri

⁵Physical Medicine and Rehabilitation, University of Missouri - Columbia, Columbia, Missouri

,

R. Scott Rector

²Department of Nutrition and Exercise Physiology, University of Missouri - Columbia, Columbia, Missouri

³NextGen Precision Health, University of Missouri - Columbia, Columbia, Missouri

⁶Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri

⁷Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri - Columbia, Columbia, Missouri

› Author Affiliations

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

Full Text

References

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