Cytokines such as
tumor necrosis factor alpha (
TNF-alpha) are key factors in liver
inflammation. Supplementation with essential omega-3
polyunsaturated fatty acids (n-3 PUFA) has been demonstrated to lower
TNF-alpha and
IL-1 production in mononuclear cells. An
inflammation-dampening effect has been observed with increased
omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabditis elegans desaturase endogenously forming
n-3 PUFA from n-6 PUFA, to analyze the effect of an increased
n-3 PUFA tissue status in the macrophage-dependent acute D-
galactosamine/lipopolysaccaride (D-GalN/LPS)
hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/
n-3 PUFA ratio as evidenced by reduced serum
alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma
TNF-alpha levels and with reduced hepatic gene expression of
TNF-alpha, IL-1beta, IFN-gamma and
IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by
DAPI-staining.
CONCLUSION: