Abstract
Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and is associated with progressive hepatocellular lipid accumulation, mostly of triglycerides, up to more than 10% of liver weight [1]
While the causes involved in the establishment of NAFLD have been largely investigated, the main factors controlling the progression of NAFLD toward non-alcoholic steatohepatitis (NASH) remain pretty much unknown and are currently intensively studied
The results showed a correlation between liver dysfunction and cognitive impairment, in particular, in the visuospatial and executive function domains, both associated with the prefrontal cortex (PFC) [23]
Summary
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and is associated with progressive hepatocellular lipid accumulation, mostly of triglycerides, up to more than 10% of liver weight [1]. This disease comprises a wide range of liver disorders, from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH) and, if not treated, can lead to threatening complications such as cirrhosis and hepatocellular carcinoma [2]. The consumption of imbalanced diets (e.g., excessive fat and sugar intake), as well as the alteration of gut microbiome are involved in NAFLD development and progression [4,5,6].
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