CuZn-SOD deficiency causes ApoB degradation and induces hepatic lipid accumulation by impaired lipoprotein secretion in mice.
Elevated hepatic reactive oxygen species play an important role in pathogenesis of liver diseases, such as alcohol-induced liver injury, hepatitis C virus infection, and nonalcoholic steatohepatitis. In the present study, we investigated and compared the hepatic lipid metabolisms of liver-specific Sod2 (superoxide dismutase 2) knock-out (Sod2 KO), Sod1 knock-out (Sod1 KO), and Sod1/liver-specific Sod2 double knock-out mice (double KO). We observed significant increases in lipid peroxidation and triglyceride (TG) in the liver of Sod1 KO and double KO mice but not in the liver of Sod2 KO mice. We also found that high fat diet enhanced fatty changes of the liver in Sod1 KO and double KO mice but not in Sod2 KO mice. These data indicated that CuZn-SOD deficiency caused lipid accumulation in the liver. To investigate the molecular mechanism of hepatic lipid accumulation in CuZn-SOD-deficient mice, we measured TG secretion rate from liver using Triton WR1339. We found significant decrease of TG secretion in CuZn-SOD-deficient mice. Furthermore, we observed marked degradation of apolipoprotein B (apoB) in the liver and plasma of CuZn-SOD-deficient mice, indicating that degradation of apoB impairs secretion of lipoprotein from the liver. Our data suggest that oxidative stress enhances hepatic lipid accumulation by impaired lipoprotein secretion due to the degradation of apoB in liver.
Uchiyama
Satoshi
S
Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Shimizu
Takahiko
T
Shirasawa
Takuji
T
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D005838:Genotype; D006505:Hepatitis / Q000378:metabolism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology*; D000099156:Superoxide Dismutase 2
D001055:Apolipoproteins B; D008074:Lipoproteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2