title: Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis.
abstract: 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(2)O(2) and key regulators of liver gluconeogenesis, glycolysis, and lipogenesis.
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zongyong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Xin Gen
authors.initials: XG
authors.lastname: Lei
mesh_terms: D000818:Animals; D055786:Gene Knockout Techniques; D005941:Glucokinase / Q000378:metabolism; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D050155:Lipogenesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1
chemical_list: C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D006003:Glycogen; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D011494:Protein Kinases; D005941:Glucokinase; D010749:Phosphoprotein Phosphatases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse