Catalase deletion promotes prediabetic phenotype in mice

Area of Science:

• Biochemistry
• Metabolic Physiology
• Genetics

Background:

• Hydrogen peroxide (H2O2) is an endogenous molecule with dual roles: toxic oxidant and signaling molecule.
• Catalase metabolizes H2O2, protecting against oxidative stress and potentially influencing cellular signaling.
• Acatalasemia is linked to an increased risk of diabetes.

Purpose of the Study:

• To investigate the role of catalase in metabolic regulation.
• To determine the phenotype of catalase knockout (Cat-/-) mice on a standard diet.

Main Methods:

• Generation and analysis of catalase knockout (Cat-/-) mice.
• Assessment of body weight, body composition, serum/hepatic lipid profiles, and glucose/insulin levels.
• Histological examination of liver and pancreas.
• RNA-sequencing (RNA-seq) analysis of hepatic gene expression.

Main Results:

• Cat-/- mice exhibited an obese phenotype with increased body weight and altered lipid deposition.
• Elevated serum and hepatic triglycerides, increased hepatic PPARγ expression, and liver steatosis with inflammation were observed.
• Pancreatic changes, impaired glucose tolerance, and elevated fasting insulin indicated a pre-diabetic status.
• RNA-seq revealed differential expression of genes related to metabolic syndrome, diabetes, and obesity.

Conclusions:

• Mice lacking catalase develop an obese, pre-diabetic phenotype.
• These findings highlight catalase's integral role in metabolic regulation.
• Catalase deficiency contributes to conditions associated with metabolic syndrome and diabetes.