title: Manganese superoxide dismutase is reduced in the liver of male but not female humans and rodents with non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is among the most common liver diseases. Oxidative stress is one of the pathogenic mechanisms contributing to the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH). Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidative enzyme and here its expression in rodent and human NAFLD has been analyzed. MnSOD is found reduced in the liver of male mice fed a high fat diet and male ob/ob mice. Female mice fed an atherogenic diet to induce NASH have MnSOD protein levels comparable to controls. In a cohort of 30 controls, 41 patients with fatty liver and 39 NASH patients, MnSOD mRNA is significantly lower in the steatotic and NASH liver. When analyzed in both genders separately reduction of MnSOD expression is only found in males. Here, MnSOD mRNA negatively correlates with steatosis grade but not with extent of fibrosis or inflammation. MnSOD is, however, not reduced in primary human hepatocytes (PHH) treated with palmitate or oleate to increase cellular triglycerides. Lipopolysaccharide, TNF, IL-6, TGFβ and leptin which are all raised in NAFLD do not affect MnSOD in PHH. Adiponectin which attenuates oxidative stress partly by increasing MnSOD in macrophages does not induce MnSOD in PHH. In summary, current data show that hepatic MnSOD is reduced in male but not female humans and rodents with NAFLD.
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, 93042 Regensburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Krautbauer
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.forename: Madeleine
authors.initials: M
authors.lastname: Lupke
authors.forename: Josef
authors.initials: J
authors.lastname: Wanninger
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hader
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D015331:Cohort Studies; D005234:Fatty Liver / Q000201:enzymology / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D013482:Superoxide Dismutase
keywords: Fatty liver; Gender; Hepatocyte; Superoxide dismutase