Catalase overexpression modulates metabolic parameters in a new 'stress-less' leptin-deficient mouse model

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Amos, Deborah L.¹  Robinson, Tanner¹  Massie, Melissa B.¹  Cook, Carla¹  Hoffsted, Alexis¹  Crain, Courtney¹  Santanam, Nalini¹ 

[1] Marshall Univ, Joan C Edwards Sch Med, Dept Biomed Sci, 1700 3rd Ave,435S BBSC, Huntington, WV 25755 USA

关键词: Obesity;    Antioxidant;    Adipokine;    Sexual dimorphism;    Oxidative stress;    Appetite regulation;   

DOI  :  10.1016/j.bbadis.2017.06.016

来源: Elsevier

【 摘 要 】

Oxidative stress plays a key role in obesity by modifying the function of important biological molecules, thus altering obesogenic pathways such as glucose and lipid signaling. Catalase, is an important endogenous antioxidant enzyme that catabolizes hydrogen peroxide produced by the dismutation of superoxide. Recent studies have shown knockdown of catalase exacerbates insulin resistance and leads to obesity. We hypothesized that overexpressing catalase in an obese mouse will modulate obesogenic pathways and protect against obesity. Therefore, we bred catalase transgenic ([Tg(CAT)(+ / -)] mice with Ob/Ob mice to generate the hybrid Bob-Cat mice. This newly generated stress-less mouse model had decreased oxidative stress (oxidized carbonylated proteins). ECHO-MRI showed lower fat mass but higher lean mass in Bob-Cat mice. Comprehensive Lab Animal Monitoring System (CLAMS) showed light and dark cycle increase in energy expenditure in Bob-Cat mice compared to wild type controls. Circulating levels of leptin and resistih showed no change. Catalase mRNA expression was increased in key metabolic tissues (adipose, liver, intestinal mucosa, and brain) of the Bob-Cat mice. Catalase activity, mRNA and protein expression was increased in adipose tissue. Expression of the major adipokines leptin and adiponectin was increased while pro-inflammatory genes, MCP-1/JE and IL-1 beta were lowered. Interestingly, sexual dimorphism was seen in body composition, energy expenditure, and metabolic parameters in the Bob-Cat mice. Overall, the characteristics of the newly generated Bob-Cat mice make it an ideal model for studying the effect of redox modulators (diet/exercise) in obesity.

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