| Summary: | 碩士 === 高雄醫學大學 === 醫學遺傳學研究所 === 99 === Obesity is a very big problem for human health. The World Health Organization indicates that the population of obesity is continuously increasing, and obesity is the major cause of metabolic syndrome, Type II diabetes and cardiovascular diseases.
Oxidative stress has been reported to play an important role in insulin resistance and type II diabetes. Oxidative stress can cause DNA damage. Among the four DNA bases, guanine is the most easily one to be oxidized by reactive oxygen species (ROS) and it will become an 8-hydroxyl-2’deoxyguanosine (8-OHdG) structure. During DNA replication, 8-OHdG will cause G:C to G:A mismatched transversion, and result in diseases or mutations. In base excision repaired pathway, both the 8-oxoguanine DNA glycosylase1 (OGG1) and Nei endonuclease VIII-like 1 (NEIL1) enzymes can recognize and remove 8-OHdG. According to a literature, knockout the NEIL1 gene resulted in metabolic syndrome in mice. However, the role of OGG1 in metabolic syndrome is not fully investigated yet. Our aim of this study is to observe the expression of OGG1 during adipogenesis of 3T3-L1 adipocytes and in the fat tissue of high-fat-diet-induced obese mice.
In our study, high-fat-diet-induced obese mice showed to have insulin resistance. The mRNA expression of insulin receptor and insulin receptor substrate-1 was decreased in the fat tissue of obese mice when compared to those of normal-diet mice. In addition, the genes (such as SOD1, OGG1 and NEIL1) related to remove oxidative stress were expressed lower in the fat tissue of obese mice. In 3T3-L1 adipocyte model, lipid accumulation and oxidative stress were increased by time. Amount of 8-OHdG was increased with lipid accumulation in adipocytes. OGG1, but not NEIL1, mRNA and protein expressions were significantly increased by time. However, the expression of OGG1 was decreased when the excess lipid accumulated in adipocytes.
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