title: 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.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. Electronic address: lorena.bavia@gmail.com.
authors.forename: Lorena
authors.initials: L
authors.lastname: Bavia
authors.affiliation: Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Juliano Bertollo
authors.initials: JB
authors.lastname: Dettoni
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Venancio Avancini
authors.initials: VA
authors.lastname: Ferreira Alves
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000068617:Genetic Background; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000276:immunology*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D003182:Complement C5; D016207:Cytokines; D018836:Inflammation Mediators; D012709:Serum Albumin; D002784:Cholesterol
keywords: C5; Cholesterol; Inflammation; Liver; NALD; Steatosis