The Testicular Leptin System in Rats with Different Severity of Type 2 Diabetes Mellitus

Abstract

Leptin is one of the major regulators of the reproductive system which targets all components of the hypothalamic—pituitary—gonadal axis. In type 2 diabetes mellitus (DM2), functions of the male reproductive system are impaired, which may be due to altered activity of the testicular leptin system. The aim of this work was to study the leptin level and the functional state of the leptin signaling system in the testes of male Wistar rats with different degrees of severity of DM2 induced by a high-fat diet and low-dose streptozotocin treatment. It was found that rats with highly severe DM2 (D-HS group) manifested marked hyperleptinemia, decreased plasma testosterone level, lower sperm count, and higher number of the abnormally shaped sperm accompanied by hyperglycemia, impaired glucose tolerance, insulin resistance, and increased levels of glycated hemoglobin and free fatty acids. The testes of this rat group had an increased leptin level, decreased number of leptin receptors, and attenuated phosphorylation of the effectory components of leptin signaling—transcription factor STAT3 at Tyr705 and Akt-kinase at Ser473. In rats with moderately severe DM2 (D-MS group), metabolic and hormonal disturbances, as well as a decrease in the plasma testosterone level and sperm abnormalities, were less pronounced. The plasma leptin level significantly exceeded that in control only after glycemic load. In the D-MS group’s testes, no statistically significant differences in levels of leptin and its receptor, as well as in STAT3 and Akt-kinase phosphorylation, were revealed compared to control. Thus, pathological changes in steroidogenesis and spermatogenesis in male rats with DM2 depend on the severity of metabolic and hormonal disturbances and the functional state of testicular leptin signaling, the severity of changes in which correlates positively with systemic hyperleptinemia.