|Göteborgs universitets publikationer
Complement C3 contributes to ethanol-induced liver steatosis in mice.
Författare och institution:
Igor Bykov (-); Sami Junnikkala (-); Marcela Pekna (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Kai O Lindros (-); Seppo Meri (-)
Annals of medicine, 38 ( 4 ) s. 280-6
Artikel, refereegranskad vetenskaplig
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.). CONCLUSION. 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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
Alanine Transaminase, blood, Animals, Complement C3, genetics, metabolism, Dietary Fats, administration & dosage, Ethanol, administration & dosage, Fatty Liver, Alcoholic, blood, metabolism, pathology, Lipid Peroxidation, Liver, metabolism, pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Size, Triglycerides, metabolism