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Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis

文献类型： 外文期刊

作者： Wang, Li 1 ; Jiang, Zongyong 2 ; Lei, Xin Gen 1 ;

作者机构： 1.Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA

2.Guangdong Acad Agr Sci, Inst Anim Sci, Minist Agr, Key Lab Anim Nutr & Feed Sci S China, Guangzhou 510640, Guangdong, Peoples R China

关键词： Antioxidant enzyme;Free radicals;Glucose;Lipid;Mouse;Reactive oxygen species

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：7.376； 五年影响因子：7.934 ）

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收录情况： SCI

摘要： We previously observed a stronger effect of knockout of Cu,Zn-superoxide dismutase (SOD1) than that of Se-dependent glutathione peroxidase 1 (GPX1) on murine body weight and glucose homeostasis. Two experiments were conducted to determine how hepatic lipid profiles and key metabolic regulators were correlated with this difference. SOD1 -/- and GPX1 -/- mice and their respective wild-type (WT) littermates (n=6 or 7/group, male) were fed a Se-adequate Torula yeast-sucrose diet and killed at 6 months of age to collect liver samples. In Experiment 1, fasted SOD1 -/- mice displayed pyruvate intolerance and a 61 decrease (P<0.05) in liver glycogen compared with their WT littermates. The former had lower (P<0.05) activities of phosphoenolpyruvate carboxykinase, total protein phosphatase, and protein phosphatase 2A, but a higher (P<0.05) activity of glucokinase in the liver than the latter. In contrast, hepatic concentrations of total cholesterol, triglycerides, and nonesterified fatty acids were increased by 11 to 100 (P<0.05) in the SOD1 -/- mice. Meanwhile, these mice had elevated (P<0.05) hepatic protein levels of sterol-regulatory element binding proteins 1 and 2, p53 MAPK, total and phosphorylated AMP-activated protein kinase α1 protein, protein tyrosine phosphatase 1B, and protein phosphatase 2B. In Experiment 2, GPX1 -/- mice and their WT littermates were compared, but showed no difference in any of the measures. In conclusion, knockout of SOD1, but not GPX1, led to a decreased liver glycogen storage synchronized with pyruvate intolerance and elevated hepatic lipid profiles in adult mice. This striking comparison was possibly due to unique impacts of these two knockouts on intracellular tone of H 2O 2 and key regulators of liver gluconeogenesis, glycolysis, and lipogenesis.

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