Nesfatin-1 Ameliorates Testicular Function Changes in Type 2 Diabetic Rats

Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a common problem that is accompanied by disturbed metabolic homeostasis, oxidative stress and increase in proinflammatory cytokines. On the other hand, normal body metabolism is essential for the testicular function. Also, nesfatin-1 is a peptide hormone produced by numerous tissues, including the testes and shared in regulation of metabolic homeostasis and had antioxidant and anti-inflammatory properties.
Aim: To investigate the effects of T2DM on testicular functions and the effects of exogenous treatment with nesfatin-1 on modulation of those effects, and, to declare the possible involved mechanisms.
Material and Methods: 24-healthy adult male albino rats with a weight of 180-200gm, were divided into three groups of 8 rats each; control, type 2 diabetic (T2DM) and nesfatin-1 treated type 2 diabetic (T2DM + Nesfatin) groups. The control group received a standard diet, while, the diabetic groups (T2DM and T2DM + Nesfatin) received a High Fat Diet (HFD). Five weeks after beginning HFD, rats were fasted for 12h and received streptozotocin, in a dose of 35mg/kg, dissolved in 0. 1M sodium citrate buffer (pH 4.5) intraperito-neally (i.p.). Then, rats of the control and T2DM groups received normal saline i.p. in a dose of 1ml/kg/day for more 4 weeks and they continued to be fed with their corresponding diet, while, those of T2DM + Nesfatin group were treated with nesfatin-1 in a dose of 2mg/kg/day i.p. for more 4 weeks and they continued to be fed with HFD. The serum levels of testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), tumor necrosis factor alpha (TNFa) and interleukin-1 beta (IL-1b) were measured in the studied groups. Also, epididymal sperm motility and count, testicular histopa-thology and antioxidant enzymes Superoxide Dismutase (SOD) and catalase (CAT) activities were examined.
Results: A significant (p<0.001) increase in the final Body Mass Index (BMI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, serum levels of glucose, insulin, Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL), TNFa  and IL-1b was found in the T2DM group in comparison to the control group. On the other hand, a significant (p<0.001) decrease in serum levels of High Density Lipoprotein (HDL), FSH, LH, and testosterone was Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a common problem that is accompanied by disturbed metabolic homeostasis, oxidative stress and increase in proinflammatory cytokines. On the other hand, normal body metabolism is essential for the testicular function. Also, nesfatin-1 is a peptide hormone produced by numerous tissues, including the testes and shared in regulation of metabolic homeostasis and had antioxidant and anti-inflammatory properties.
Aim: To investigate the effects of T2DM on testicular functions and the effects of exogenous treatment with nesfatin-1 on modulation of those effects, and, to declare the possible involved mechanisms.
Material and Methods: 24-healthy adult male albino rats with a weight of 180-200gm, were divided into three groups of 8 rats each; control, type 2 diabetic (T2DM) and nesfatin-1 treated type 2 diabetic (T2DM + Nesfatin) groups. The control group received a standard diet, while, the diabetic groups (T2DM and T2DM + Nesfatin) received a High Fat Diet (HFD). Five weeks after beginning HFD, rats were fasted for 12h and received streptozotocin, in a dose of 35mg/kg, dissolved in 0. 1M sodium citrate buffer (pH 4.5) intraperito-neally (i.p.). Then, rats of the control and T2DM groups received normal saline i.p. in a dose of 1ml/kg/day for more 4 weeks and they continued to be fed with their corresponding diet, while, those of T2DM + Nesfatin group were treated with nesfatin-1 in a dose of 2mg/kg/day i.p. for more 4 weeks and they continued to be fed with HFD. The serum levels of testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), tumor necrosis factor alpha (TNFa) and interleukin-1 beta (IL-1b) were measured in the studied groups. Also, epididymal sperm motility and count, testicular histopa-thology and antioxidant enzymes Superoxide Dismutase (SOD) and catalase (CAT) activities were examined.
Results: A significant (p<0.001) increase in the final Body Mass Index (BMI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, serum levels of glucose, insulin, Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL), TNFa  and IL-1b was found in the T2DM group in comparison to the control group. On the other hand, a significant (p<0.001) decrease in serum levels of High Density Lipoprotein (HDL), FSH, LH, and testosterone was reported in T2DM group in comparison to the control group. Also, a significant (p<0.001) decline in right testis weight, testicular SOD and CAT activity, and, epididymal sperm motility and count was found in T2DM group in comparison to the control group. Also, in T2DM group, a significant negative correlation between testicular functions (serum testosterone, epididymal sperm count and epididymal sperm motility) and each of final BMI, HOMA-IR, serum levels of IL-1b and TNFa, and, testicular SOD and CAT activity, was reported. After exogenous nesfatin-1 treatment, the changes noticed in T2DM group were reversed as a significant (p<0.001) decrease in final BMI, HOMA-IR index, serum levels of glucose, insulin, TC, TG, TNFa  and IL-1b was found in the T2DM+Nesfatin group in comparison to the T2DM group. On the other hand, a significant (p<0.001) increase in serum levels of HDL, FSH, LH, and testosterone in the T2DM + Nesfatin group was recorded in comparison to the T2DM group. Also, a significant (p<0.001) rise in right testis weight, testicular SOD and CAT activity, and, epididymal sperm motility and count was found in the T2DM + Nesfatin group when compared with T2DM group.
Conclusion: T2DM decreased testicular functions, sper-matogenesis and steroidogenesis, through disturbing metabolic homeostasis, decreasing the gonadotropins secretion, reducing testicular antioxidant activity and increasing proinflammatory cytokines. On the other hand, exogenous nesfatin-1 treatment ameliorated testicular function changes in T2DM through controlling body weight, improving metabolic disturbances, increasing FSH and LH secretion, its antioxidant and its anti-inflammatory properties.