The complement component C5 promotes liver steatosis and inflammation in murine non-alcoholic liver disease model.

Abstract Non-Alcoholic Fatty Liver Disease (NALD) is considering a hepatic manifestation of metabolic syndrome. Although the pathogenesis of NALD is not completely understood, insulin resistance and inflammatory cytokines are implicated. Considering that component C5 is a central mediator of inflammation, we investigated the role of C5 in the establishment of NALD. Eight to ten-week old B6 C5 + and A/J C5 − male mice were fed a high fat diet containing glucose (HFDG) for 6 and 10 weeks. We observed that B6 C5 + mice HFDG-fed for 10 weeks developed hepatomegaly, triglycerides (TG) accumulation, steatosis and enhanced liver TNF-α, IL-6, IL-12p70 and IL-17 levels when compared to A/J C5 − mice. Next, B6 C5 + mice were compared with congenic B6 C5 − mice. Again, B6 C5 + HFDG-fed mice developed more steatosis, liver centro-lobular inflammation and presented higher levels of liver IL-1β, IL-12p70, IL-17 and TFG-β than B6 C5 − mice under the same conditions. B6 C5 + mice HFDG-fed also presented lower concentrations of serum albumin, serum cholesterol, blood leukocytes and liver NO production when compared with B6 C5 − mice. We concluded that murine C5 contributes effectively to liver steatosis and inflammation in NALD pathogenesis. In addition, C5 is also important to control serum cholesterol and albumin levels in the C57BL/6 genetic background.