Figure 2.

Cross-talk of myeloid-derived cells from different compartments in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Inflammatory activation promoting the progression of NAFLD involves the interaction between liver, gut, and adipose tissue. From the gastrointestinal tract (left lower corner), pathogen-associated-molecular-patterns (PAMPs) enter the circulation due to increased intestinal permeability and promote hepatic inflammation together with local danger-associated-molecular-patterns (DAMPs). In adipose tissue (right lower corner), chronic inflammation induces the release of pro-inflammatory cytokines (e.g., IL-6, TNF-α) and free fatty acids (FFA) that trigger hepatic injury and activation of hepatic macrophages such as monocyte-derived macrophages (MoMFs) and tissue-resident Kupffer cells (KCs). Activated macrophages in the liver produce CCL2 (and other pro-inflammatory cytokines) to recruit circulating monocytes from the blood that contribute to sustained inflammation. ATMs, adipose tissue macrophages; DCs, dendritic cells; EV, extracellular vesicles; LPS, lipopolysaccharide; MPO, myeloperoxidases; NFs, neutrophils; SFA, saturated fatty acids.