Investigation of effect of dietary high-fructose on insulin signaling pathway, inflammation and apoptosis in testis of rats

Fructose consumption-induced metabolic syndrome leads to insulin resistance in various tissues as well as causing tissue damage due to triggering inflammatory and apoptotic pathways. Studies showed that there was a relationship between insulin resistance and low testosterone levels in infertile men. However, effect of high-fructose consumption on the male reproductive system has been insufficiently documented. The relationship between inflammation and apoptosis has not been sufficiently investigated in high fructose diet-induced metabolic syndrome as well as Blood-Testis Barrier proteins and insulin signaling pathway. Therefore, a metabolic syndrome model was produced by giving fructose to the rats as 20% solution in drinking water for 15 weeks. In this thesis, the effects of high-fructose diet on metabolic parameters, testicular inflammatory, apoptotic factors, insulin signaling pathway, Blood-Testis Barrier proteins and histological changes were investigated by using suitable methods. Fructose consumption increased rat plasma glucose, triglyceride and insulin levels, whereas free and total testosterone levels were significantly reduced in testicular tissue of the rats. Inflammatory molecules such as TNFα and IL-1β levels were increased in testicular tissue of fructose-treated rats. This dietary intervention decreased insulin signaling molecules including IRS-1, IRS-2, PI3K, mTOR and eNOS mRNA expressions and protein levels in testicular samples of rats. In addition, IR, p-Akt, p-eNOS and SIRT1 protein levels as well as p-Akt/Akt and p-eNOS/eNOS ratios were decrease in testicular tissue of fructose-treated rats. Also, It was determined that claudin11 and N-cadherin levels of Blood-Testis Barrier proteins were decreased with fructose diet. Moreover, dietary fructose suppressed anti-apoptotic Bcl-2 mRNA and protein expressions. In immunohistochemical staining, high fructose consumption was shown to reduce spermatogonial p53 and caspase8 levels. Hematoxylin-Eosin staining showed that testicular degeneration was occurred in the rats due to intake of high-fructose diet. Consequently, high fructose consumption caused inflammation and apoptosis as well as suppressed Blood-Testis Barrier and insulin signaling pathway proteins in testicular tissue of rat. Thus, for the first time, this study explored the effects of fructose consumption on testicular inflammatory, apoptotic and insulin signaling pathways.