in AFLD, the authors suggested that C3a binding to the receptor C3aR, which is highly expressed on Kupffer cells, can promote the inflammatory response and stimulate the release of the inflammatory cytokine tumor necrosis factor-α (TNF-α). TNF-α participates in AFLD, either directly or indirectly, through the induction of insulin resistance [5]. Pritchard et al. [28] also proved that C3–/– mice did not develop AFLD or increase triglycerides in the circulation, but the levels of serum alanine aminotransferase (ALT) and inflammatory cytokines were significantly higher. On the contrary, C5–/– mice had increased hepatic triglycerides and developed AFLD, whereas they did not show increased levels of ALT or inflammatory cytokines after ethanol feeding. Another study showed that more cholesterol was deposited in the liver of C5–/– mice than in the liver of C5+/+ mice, and C5–/– mice had higher levels of serum triglycerides and cholesterol than C5+/+ mice [23]. These results show that C3 and C5 play different roles in the development of AFLD. However, the mechanisms by which the complement system is involved in AFLD are still incompletely understood.
