Effect of Cellular Senescence on Insulin Resistance in Diet-induced Obese Wistar Rats

Cellular senescence has been known as a tumor suppressor mechanism; however, some evidence shows that cellular senescence is an inducer factor for metabolic disorders, such as insulin resistance and diabetes. In this study, the effect of senescence was assayed in the peripheral tissues of diet-induced obese rats. 30 male 5-week old wistar rats were randomly assigned into high-calorie diet through 416 kcal/100 g (researcher made) or control diet for 12 weeks. Weight changes, lipid profile, glucose, insulin levels and QUICKI (Quantitative Insulin Sensitivity Check Index) index were measured at the end of the 12th week. Also the tissue samples were isolated, and immune-blotting was performed to identify proteins P16INK4a and P53 (cell senescence markers). P53 levels in the fat tissue and other peripheral tissues of obese rats were significantly higher compared to the control group. P16INK4a expression was increased only in fat tissue but protein was not expressed in other tissues. In the obese rats, the serum levels of glucose (183/60±34/90 vs. 152/40±15/48 P=0.019), cholesterol (60/70±6/88 vs.46/60±7/82 P<0.001) and triglyceride (124/60±46/43 vs. 57/20±24/02 P<0.001) were more than in the control group but The QUICKI index was significantly lower in the obese rats compared to the control group (p=0.01). Our results suggest that cell senescence in fat tissue can be predisposed to the development of insulin resistance and age-related diseases by generating some alternation in the fat tissue.