From nonalcoholic fatty liver disease to neuroinflammation: the role of chronic systemic inflammation

Neuroinflammation is a significant contributor to neurological disorders. While previous research has mainly concentrated on lesions within the brain, the potential influence of nonalcoholic fatty liver disease (NAFLD) on neuroinflammation has been largely overlooked. An increasing amount of evidence suggests that heightened chronic systemic inflammation linked to NAFLD could significantly contribute to the initiation and advancement of neuroinflammation, nonetheless, the underlying mechanisms remain unclear. This review summarizes the primary causes of chronic systemic inflammation in the context of NAFLD, delineates the mechanisms by which chronic systemic inflammation leads to neuroinflammation, analyzes the key pathways through which circulating inflammatory mediators travel from the periphery to the central nervous system and their effects on glial cells, and finally discusses the novel approaches for treating neuroinflammation via a liver-brain inflammation axis perspective. This research intends to offer an in-depth insight into how chronic systemic inflammation contributes to the connection between NAFLD and neuroinflammation.