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

First Author  Amos DL Year  2017
Journal  Biochim Biophys Acta Volume  1863
Issue  9 Pages  2293-2306
PubMed ID  28645653 Mgi Jnum  J:256222
Mgi Id  MGI:6105720 Doi  10.1016/j.bbadis.2017.06.016
Citation  Amos DL, et al. (2017) Catalase overexpression modulates metabolic parameters in a new 'stress-less' leptin-deficient mouse model. Biochim Biophys Acta 1863(9):2293-2306
abstractText  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 resistin 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-1beta 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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