Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice
A Ranjan1, M Choubey1, T Yada2,3
1Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
Purpose:
The present study was aimed to demonstrate the recuperative effect of nesfatin-1 on testicular dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced type-2 diabetes mellitus (T2DM) mice.
Method And Results:
Three experimental groups were formed: (1) vehicle control (VC), (2) T2DM mice, (3) T2DM + nesf-1. The mice with blood glucose level higher than 300 mg/dL following HFD and a single dose of STZ were used for the experiment. The T2DM mice showed increases in body mass, blood glucose and insulin levels, reductions in spermatogenesis and steroidogenesis, production of antioxidative enzymes, and disturbed lipid profile. These alterations were all ameliorated by administration of nesfatin-1 at 20 μg/Kg BW for 15 days. Nesfatin-1 treatment also increased the production of testosterone (T), improved insulin sensitivity, and effectively ameliorated the testicular aberrations, and increased spermatogenesis and steroidogenesis. In addition, nesfatin-1 treatment upregulated the PCNA and Bcl2 expression and inhibited the caspase-3 and prohibitin expression in T2DM mice. Nesfatin-1 increased insulin receptor (IR) and GLUT8 expressions, and lactate production, the changes that further substantiate the increase of energy influx to the testis.
Conclusion:
Altogether, the results suggest the ameliorative effect of nesfatin-1 against T2DM-associated testicular dysfunctions and improved insulin sensitivity along with promoting T production and fertility in T2DM mice.
Insights
Nesfatin-1 treatment improved testicular function in mice with type-2 diabetes mellitus (T2DM) induced by a high-fat diet and streptozotocin. This peptide therapy enhanced insulin sensitivity, testosterone production, and fertility, counteracting T2DM-related testicular damage.
Area of Science:
- Endocrinology
- Reproductive Biology
- Metabolic Disorders
Background:
- Type-2 diabetes mellitus (T2DM) is associated with significant testicular dysfunction.
- High-fat diet (HFD) and streptozotocin (STZ) are commonly used to induce T2DM in animal models.
- T2DM-induced testicular dysfunction impacts spermatogenesis, steroidogenesis, and overall reproductive health.
Purpose of the Study:
- To investigate the potential recuperative effects of nesfatin-1 on testicular dysfunction in HFD/STZ-induced T2DM mice.
- To evaluate nesfatin-1's impact on key markers of testicular health and metabolic parameters.
Main Methods:
- Establishment of T2DM in mice using HFD and a single dose of STZ.
- Administration of nesfatin-1 (20 μg/Kg BW for 15 days) to T2DM mice.
- Assessment of body mass, blood glucose, insulin levels, lipid profile, spermatogenesis, steroidogenesis, and specific gene/protein expressions (PCNA, Bcl2, caspase-3, prohibitin, insulin receptor, GLUT8).
Main Results:
- Nesfatin-1 treatment ameliorated HFD/STZ-induced increases in body mass, blood glucose, and insulin levels.
- Nesfatin-1 administration improved spermatogenesis, steroidogenesis, and testosterone production.
- Nesfatin-1 upregulated antioxidant enzymes, improved insulin sensitivity, and normalized lipid profiles, while modulating key protein expressions.
Conclusions:
- Nesfatin-1 demonstrates significant ameliorative effects against T2DM-associated testicular dysfunction.
- The peptide enhances insulin sensitivity, promotes testosterone production, and improves fertility in T2DM mice.
- Nesfatin-1 may represent a therapeutic agent for managing reproductive complications of T2DM.
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