Glutathione peroxidase 3 (GPx3) accounts for the major antioxidant activity in the plasma. Here, we demonstrate that down-regulation of GPx3 in the plasma of obese subjects is associated with adipose GPx3 dysregulation, resulting from the increase of inflammatory signals and oxidative stress. Although GPx3 was abundantly expressed in kidney, lung, and adipose tissue, we observed that GPx3 expression was reduced selectively in the adipose tissue of several obese animal models as decreasing plasma GPx3 level. Adipose GPx3 expression was greatly suppressed by prooxidative conditions such as high levels of TNFalpha and hypoxia. In contrast, the antioxidant N-acetyl cysteine and the antidiabetic drug rosiglitazone increased adipose GPx3 expression in obese and diabetic db/db mice. Moreover, GPx3 overexpression in adipocytes improved high glucose-induced insulin resistance and attenuated inflammatory gene expression whereas GPx3 neutralization in adipocytes promoted expression of proinflammatory genes. Taken together, these data suggest that suppression of GPx3 expression in the adipose tissue of obese subjects might constitute a vicious cycle to expand local reactive oxygen species accumulation in adipose tissue potentially into systemic oxidative stress and obesity-related metabolic complications.
Background and Aims: Epidemiologic studies provide evidence for a link between obesity or diabetes and the risk for colorectal cancer. However, there is a lack of information about the relationship between metabolic syndrome and colorectal adenoma. Therefore, we investigated whether metabolic syndrome is a risk factor for colorectal adenoma. Methods: We did a study for consecutive subjects who underwent colonoscopy as a screening exam at the Center for Health Promotion, Samsung Medical Center, from March 2004 to December 2005. According to the modified ATP III criteria, metabolic syndrome was diagnosed. We classified a total of 2,531 subjects into the adenoma group (n = 731) and the control group (n = 1,800), including normal colonoscopic finding, nonpolyp benign lesions, or histologically confirmed hyperplastic polyp.
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