title: Catalase deletion promotes prediabetic phenotype in mice.
abstract: Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat-/-) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat-/-mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat-/-mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Heit
authors.affiliation: Department of Environmental Health Services, Yale School of Public Health, Yale University, 60 College St, New Haven CT 06520-8034, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Marshall
authors.affiliation: Department of Environmental Health Services, Yale School of Public Health, Yale University, 60 College St, New Haven CT 06520-8034, USA.
authors.forename: Surrendra
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biostatistics, Yale School of Public Health, Yale University, New Haven CT 06520, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Environmental Health Services, Yale School of Public Health, Yale University, 60 College St, New Haven CT 06520-8034, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Charkoftaki
authors.affiliation: Department of Biostatistics, Yale School of Public Health, Yale University, New Haven CT 06520, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, School of Medicine University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
authors.forename: Kristofer S
authors.initials: KS
authors.lastname: Fritz
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Thompson
authors.affiliation: Department of Environmental Health Services, Yale School of Public Health, Yale University, 60 College St, New Haven CT 06520-8034, USA. Electronic address: vasilis.vasiliou@yale.edu.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D018149:Glucose Intolerance; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology; D009929:Organ Size; D018384:Oxidative Stress; D010641:Phenotype; D011236:Prediabetic State / Q000201:enzymology* / Q000235:genetics
chemical_list: D002374:Catalase
keywords: Catalase; Diabetes; Metabolism; Obesity; Steatosis