Pinto-García, Luis José; Nájera, Nayelli; Flores-Estrada, José Javier; Cáceres-Carranza, Fernando Javier

ABSTRACT

Nonalcoholic Fatty Liver Disease (NAFLD) is a prevalent global disease, affecting at least a third of the world population and having an estimated prevalence that could be greater than 50% in Mexico. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, generally associated with metabolic disorders such as obesity, type 2 diabetes, and cardiovascular disease. Kupffer cells are specialized hepatic macrophages essential for liver health and immune regulation but become pathogenic in NAFLD and contribute to liver inflammation and fibrosis through cytokine secretion and signaling pathways such as the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and the Peroxisomes Proliferators Activated Receptors Gamma (PPAR-γ). Chronic macrophage activation in NAFLD is influenced by factors such as saturated fatty acids, leading to polarization of the M1 phenotype and promoting inflammation. Currently, there are no FDA-approved drugs specifically targeting macrophage dysfunction. However, several therapeutic approaches are under investigation that may indirectly influence macrophage activation and further polarization to suppress inflammation and prevent disease progression. Promising strategies include modifying this macrophage polarization and targeting specific signaling pathways. Targeting chemokines such as the chemokine ligand 16 (CXCL16) also can potentially reduce liver inflammation and steatohepatitis. Targeting hepatic macrophage activation offers a promising approach for mitigating NAFLD progression.

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