Complement C3 contributes to ethanol-induced liver steatosis in mice.
BACKGROUND
It is becoming increasingly clear that liver steatosis, a typical early consequence of alcohol exposure, sensitizes the liver to more severe inflammatory and fibrotic changes. On the other hand, activation of the key complement component C3, a central player in causing inflammation and tissue damage, is also known to be involved in the regulation of lipid metabolism. This prompted us to study the development of alcoholic liver steatosis in mice lacking C3 (C3-/-).


RESULTS
Both C3-/- and normal C3+/+ mice were fed a steatosis-promoting high-fat diet with or without ethanol for 6 weeks. The diet without ethanol caused moderate liver steatosis in C3-/- but not in C3+/+ mice. As expected, ethanol-containing diet caused marked macrovesicular steatosis and increased the liver triglyceride content in C3+/+ mice. In contrast, ethanol diet tended to reduce steatosis and had no further effect on liver triglycerides in C3-/- mice. Furthermore, while in normal mice ethanol significantly increased the liver/body weight ratio, liver malondialdehyde level and serum alanine aminotransferase (ALT) activity, these effects were absent or small in C3-/- mice. A separate experiment with mice on chow diet confirmed the aberrant steatotic effect of ethanol in C3-/-mice: 4 hours after acute dosing of ethanol the liver triglyceride level had increased by 138% in C3+/+ mice (P<0.001), but only by 64% in C3-/- mice (n.s.).


CONCLUSIONS
In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences.
Bykov
Igor
I
National Public Health Institute, Department of Mental Health and Alcohol Research, and Department of Bacteriology and Immunology, Helsinki University Central Hospital, Finland.
Junnikkala
Sami
S
Pekna
Marcela
M
Lindros
Kai O
KO
Meri
Seppo
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D014280:Triglycerides / Q000378:metabolism
D003176:Complement C3; D004041:Dietary Fats; D014280:Triglycerides; D000431:Ethanol; D000410:Alanine Transaminase