Catalase overexpression modulates metabolic parameters in a new ‘stress-less’ leptin-deficient mouse model
| Autor: | Carla Cook, Tanner Robinson, Deborah Amos, Nalini Santanam, Melissa Massie, Alexis Hoffsted, Courtney Crain |
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| Rok vydání: | 2017 |
| Předmět: |
Leptin
0301 basic medicine medicine.medical_specialty Interleukin-1beta Mice Obese Adipokine Adipose tissue 030209 endocrinology & metabolism medicine.disease_cause Gene Expression Regulation Enzymologic Article Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Internal medicine medicine Animals Molecular Biology Chemokine CCL2 biology Adiponectin Chemistry Catalase medicine.disease Mice Mutant Strains Oxidative Stress 030104 developmental biology Endocrinology Organ Specificity biology.protein Molecular Medicine Resistin Oxidative stress |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863:2293-2306 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2017.06.016 |
| Popis: | 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 mouse. 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-1β 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. |
| Databáze: | OpenAIRE |
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