Impact of nonalcoholic fatty liver disease-related metabolic state on depression

Nonalcoholic fatty liver disease (NAFLD), also recently referred as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by hepatocyte steatosis in the setting of metabolic risk conditions and in the absence of an underlying precursor, for instance alcohol consumption, hepatotropic viruses and hepatotoxic drugs. A possible association between NAFLD and depression has been proposed, owing to intersecting pathophysiological pathways. This narrative review aimed to summarize the current evidence that illustrate the potential pathophysiological and clinical linkage between NAFLD-related metabolic state and depression. Prefrontal cortex lesions are suggested to be a consequence of liver steatosis-associated systematic hyperinflammatory state, a phenomenon also occurring in depression. In addition, depressive symptoms are present in neurotransmitter imbalances. These abnormalities seem to be correlated with NAFLD/MAFLD, in terms of insulin resistance (IR), ammonia and gut dysbiosis' impact on serotonin, dopamine, noradrenaline levels and gamma aminobutyric acid receptors. Furthermore, reduced levels of nesfatin-1 and copine-6-associated BDNF (brainderived neurotrophic factor) levels have been considered as a probable link between NAFLD and depression. Regarding NAFLD-related gut dysbiosis, it stimulates mediators including lipopolysaccharides, short-chain fatty acids and bile acids, which play significant role in depression. Finally, western diet and IR, which are mainstay components of NAFLD/MAFLD, are, also, substantiated to affect neurotransmitters in hippocampus and produce neurotoxic lipids that contribute to neurologic dysfunction, and thus trigger emotional disturbances, mainly depressive symptoms.

Automated summary

Nonalcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by liver cell steatosis in the absence of underlying factors such as alcohol consumption, hepatotropic viruses, and hepatotoxic drugs. There is evidence suggesting a possible link between NAFLD/MAFLD and depression, with overlapping pathophysiological pathways. These include prefrontal cortex lesions, neurotransmitter imbalances, insulin resistance (IR), gut dysbiosis, and altered levels of certain biomarkers. Western diet and IR, which are main components of NAFLD/MAFLD, can also affect neurotransmitters and contribute to emotional disturbances, particularly depressive symptoms.