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Free Radic Biol Med. 2017 Feb;103:48-56. doi: 10.1016/j.freeradbiomed.2016.12.011. Epub 2016 Dec 8.

Catalase deletion promotes prediabetic phenotype in mice.

Author information

1
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
2
Department of Environmental Health Services, Yale School of Public Health, Yale University, 60 College St, New Haven CT 06520-8034, USA.
3
Department of Biostatistics, Yale School of Public Health, Yale University, New Haven CT 06520, USA.
4
Department of Pathology, School of Medicine University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
5
Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, CO 80045, USA.
6
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.

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.

KEYWORDS:

Catalase; Diabetes; Metabolism; Obesity; Steatosis

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