Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Ave., Huntington, WV 25755-0001, United States.
Biochim Biophys Acta Mol Basis Dis. 2017 Sep;1863(9):2293-2306. doi: 10.1016/j.bbadis.2017.06.016. Epub 2017 Jun 20.
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-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.
氧化应激通过改变葡萄糖和脂质信号等肥胖相关途径的重要生物分子功能在肥胖中起关键作用。过氧化氢酶是一种重要的内源性抗氧化酶，可分解超氧化物歧化产生的过氧化氢。最近的研究表明，过氧化氢酶的敲低会加剧胰岛素抵抗并导致肥胖。我们假设在肥胖小鼠中过表达过氧化氢酶将调节肥胖相关途径并预防肥胖。因此，我们将过氧化氢酶转基因 ([Tg(CAT)] 小鼠与 Ob/Ob 小鼠杂交，生成杂交“Bob-Cat”小鼠。这种新生成的“无应激”小鼠模型的氧化应激（氧化的羰基化蛋白）降低。ECHO-MRI 显示“Bob-Cat”小鼠的脂肪量减少但瘦肉量增加。综合实验室动物监测系统 (CLAMS) 显示 Bob-Cat 小鼠与野生型对照相比，在光照和黑暗周期中能量消耗增加。循环中的瘦素和抵抗素水平没有变化。Bob-Cat 小鼠的关键代谢组织（脂肪、肝脏、肠黏膜和大脑）中过氧化氢酶 mRNA 表达增加。脂肪组织中过氧化氢酶活性、mRNA 和蛋白表达增加。主要脂肪因子瘦素和脂联素的表达增加，而促炎基因 MCP-1/JE 和 IL-1β 的表达降低。有趣的是，Bob-Cat 小鼠的身体成分、能量消耗和代谢参数存在性别二态性。总的来说，新生成的“Bob-Cat”小鼠的特征使其成为研究氧化还原调节剂（饮食/运动）在肥胖中的作用的理想模型。
