title: Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice.
abstract: OBJECTIVE
  The complement pathway is an important component of the innate and adaptive immune response. Here we tested the hypothesis that activation of complement is required for development of ethanol-induced fatty liver.
  
  
  METHODS
  Wild-type mice and mice lacking the third (C3) or fifth (C5) components of the complement activation pathway, as well as mice lacking decay-accelerating factor (CD55/DAF), a complement regulatory protein, were fed Lieber-DeCarli ethanol-containing diets for 6 weeks or pair-fed control diets.
  
  
  RESULTS
  Ethanol feeding to wild-type mice increased C3a in plasma. Wild-type and C5-/- mice fed the ethanol diet developed hepatic steatosis characterized by microvesicular and macrovesicular lipid accumulation and increased triglyceride content. C3-/- mice did not develop steatosis, while CD55/DAF-/- mice accumulated even more hepatic triglyceride after ethanol feeding than wild-type mice. Levels of serum alanine aminotransferase and hepatic tumor necrosis factor alpha, indicators of hepatocyte injury and inflammation, respectively, were increased in wild-type and CD55/DAF-/- mice but not in C5-/- mice after ethanol feeding. In contrast to the protective effect of C3-/- against ethanol-induced steatosis, levels of both alanine aminotransferase and tumor necrosis factor alpha were increased in C3-/- mice after ethanol feeding.
  
  
  CONCLUSIONS
  Here we have identified several elements of the complement system as important contributors to ethanol-induced fatty liver. C3 contributed primarily to the accumulation of triglyceride in the liver, whereas C5 was involved in inflammation and injury to hepatocytes. Further, the absence of CD55/DAF exacerbated these responses, suggesting that CD55/DAF serves as a barrier to ethanol-induced fatty liver.
authors: Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106-4906.|Pathology, Western Reserve University, Case Cleveland, OH 44106-4906.
authors: Michele T
authors: MT
authors: Pritchard
authors: Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106-4906.|Pathology, Western Reserve University, Case Cleveland, OH 44106-4906.
authors: Megan R
authors: MR
authors: McMullen
authors: Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106-4906.
authors: Abram B
authors: AB
authors: Stavitsky
authors: Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106-4906.
authors: Jessica I
authors: JI
authors: Cohen
authors: Pathology, Western Reserve University, Case Cleveland, OH 44106-4906.
authors: Feng
authors: F
authors: Lin
authors: Pathology, Western Reserve University, Case Cleveland, OH 44106-4906.
authors: M
authors: M
authors: Edward Medof
authors: Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106-4906.
authors: Laura E
authors: LE
authors: Nagy
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000097:blood; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015926:Complement C3a / Q000378:metabolism; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D004195:Disease Models, Animal; D004790:Enzyme Induction; D000431:Ethanol / Q000097:blood; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018958:CD55 Antigens; D002492:Central Nervous System Depressants; D003176:Complement C3; D003182:Complement C5; D015850:Interleukin-6; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D015926:Complement C3a; D007371:Interferon-gamma; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase