ABSTRACT
Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.
Subject(s)
Animals , Humans , Male , Mice , AMP-Activated Protein Kinases , Metabolism , Antioxidants , Pharmacology , Autophagy , Cells, Cultured , Endothelial Cells , Mice, Inbred C57BL , Oxidative Stress , Reactive Oxygen Species , Metabolism , Resveratrol , Pharmacology , Signal Transduction , TOR Serine-Threonine Kinases , MetabolismABSTRACT
<p><b>BACKGROUND</b>Insulin resistance (IR) plays an important pathophysiological role in the development of diabetes, dyslipidemia, hypertension, and cardiovascular disease. Moreover, IR can occur even in non-obese people without diabetes. However, direct detection of IR is complicated. In order to find a simple surrogate marker of IR early in non-obese people, we investigate the association of commonly-used biochemical markers (liver enzymes and lipid profiles) with IR in urban middle-aged and older non-obese Chinese without diabetes.</p><p><b>METHODS</b>This cross-sectional study included 1 987 subjects (1 473 women). Fasting blood samples were collected for measurement of glucose, insulin, liver enzymes, lipid profiles and creatinine. Subjects whose homeostasis model of assessment-IR (HOMA-IR) index values exceeded the 75th percentile (2.67 for women and 2.48 for men) of the population were considered to have IR. The area under the receiver operating characteristic curve (ROC) was used to compare the power of potential markers in identifying IR.</p><p><b>RESULTS</b>Triglycerides (TG) and ratio of TG to high-density lipoprotein cholesterol (TG/HDL-C) discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic (ROC) curves (AUC) values were 0.770 (95% confidence interval 0.733-0.807) and 0.772 (0.736-0.809), respectively, for women and 0.754 (0.664-0.844) and 0.756 (0.672-0.840), respectively, for men. To identify IR, the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L (sensitivity 74.3%, specificity 71.0%) and 0.873 (sensitivity 70.1%, specificity 73.4%), respectively, for women, and 1.275 mmol/L (sensitivity 66.7%, specificity 74.4%) and 0.812 (sensitivity 75.8%, specificity 69.2%), respectively, for men.</p><p><b>CONCLUSION</b>TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.</p>