Hepatic gene expression and lipid parameters in complement C3(-/-) mice that do not develop ethanol-induced steatosis.
J Hepatol
; 46(5): 907-14, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17321001
ABSTRACT
BACKGROUND/AIMS:
Fatty infiltration initiates alcohol-induced liver changes and complement component C3 affects lipid metabolism. We recently observed that ethanol-induced steatosis seen in normal (C3(+/+)) mice was absent in livers of C3-deficient (C3(-/-)) mice. To understand the underlying molecular mechanisms we analyzed lipid parameters and liver gene expression profiles in these mice.METHODS:
A Western-type high-fat diet with ethanol or carbohydrates (control) was fed for 6 weeks to C3(+/+) and C3(-/-) mice. Serum and liver lipid parameters were analyzed and liver mRNA expression patterns studied by micro-array analysis and RT-PCR.RESULTS:
In both genotypes ethanol markedly reduced serum cholesterol, apolipoprotein A-I, phospholipid transfer protein activity and hepatic mRNA levels of fatty acid-binding proteins and fatty acid beta-oxidation enzymes. In contrast, exclusively in C3(-/-) mice, ethanol treatment increased serum and liver adiponectin levels but down-regulated transcripts of lipogenic enzymes, adiponectin receptor 2 and adipose differentiation-related protein and up-regulated phospholipase D1.CONCLUSIONS:
We propose that these ethanol-induced alterations observed exclusively in C3(-/-) mice contribute to protection against fatty infiltration and subsequent inflammatory processes in the liver of these mice. The results suggest important cross-talk between complement factor C3 and lipid regulators in ethanol-induced steatosis.
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Base de dados:
MEDLINE
Assunto principal:
Complemento C3
/
Expressão Gênica
/
Fígado Gorduroso Alcoólico
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
J Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Finlândia