1-DNJ Alleviates Obesity-Induced Testicular Inflammation in Mice Model by Inhibiting IKKβ/ NF-kB Pathway

Wenli Mai1, Yi Shang2, Yibin Wang3

  • 1Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Sichuan, 637000, China.

Insights

1-Deoxynojirimycin (1-DNJ) from mulberry leaves reduces obesity-induced inflammation and improves male fertility in mice. This natural compound alleviates testicular damage and enhances sperm health by inhibiting the IKKβ/NF-kB pathway.

Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Inflammation Research

Background:

  • Obesity is linked to chronic inflammation, negatively impacting male reproductive health and fertility.
  • The role of 1-Deoxynojirimycin (1-DNJ), an alkaloid from mulberry leaves, in addressing obesity-related male infertility is not well understood.
  • Investigating 1-DNJ's potential to counteract obesity-induced inflammation affecting male fertility is crucial.

Purpose of the Study:

  • To explore the mechanism by which 1-DNJ mitigates fertility impairment in male mice with obesity-induced inflammation.
  • To assess the effects of 1-DNJ on metabolic profiles, reproductive capacity, and testicular health in obese mice.
  • To determine if 1-DNJ can inhibit the IKKβ/NF-kB signaling pathway and reduce inflammation.

Main Methods:

  • Male mice were induced into obesity using a high-fat diet (HFD) and treated with 1-DNJ or metformin for 8 weeks.
  • Metabolic profiles, sperm parameters (viability, motility, count), and testicular histology were evaluated.
  • Inflammatory markers (TNFα, IL-1β, IL-6) and the IKKβ/NF-kB pathway activation were assessed via biochemical assays and western blotting.

Main Results:

  • HFD-induced obesity led to lipid metabolism disorders, decreased testosterone, impaired sperm motility, and elevated inflammatory markers.
  • 1-DNJ treatment improved testosterone levels, ameliorated testicular damage, and enhanced sperm viability in obese mice.
  • 1-DNJ effectively inhibited the IKKβ/NF-kB signaling pathway, significantly reducing inflammation in obese male mice.

Conclusions:

  • 1-Deoxynojirimycin (1-DNJ) demonstrates potential in improving male fertility by reducing obesity and associated inflammation.
  • 1-DNJ's anti-inflammatory action, mediated through the inhibition of the IKKβ/NF-kB pathway, is key to its beneficial effects.
  • These findings suggest 1-DNJ as a promising therapeutic agent for male infertility linked to obesity and inflammation.