Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration

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.

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“…Research findings have indicated that MASLD exhibits a correlation with an elevated susceptibility to cerebrovascular complications [9,119]. This association subsequently contributes to the occurrence of neurodegenerative alterations within the brain and an augmented likelihood of developing dementia [120,121]. Critical to physiological nitric oxide (NO) production is endothelial nitric oxide synthase (eNOS), an enzyme that is primarily found in the endothelium of blood vessels [122].…”

The brain-liver cholinergic anti-inflammatory pathway and viral infections

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