关键词: 1-DNJ Inflammatory factors NF-kB Obesity Reproductive ability

Mesh : Animals Male Obesity / metabolism complications I-kappa B Kinase / metabolism NF-kappa B / metabolism Mice Signal Transduction / drug effects Inflammation / metabolism Testis / drug effects metabolism pathology Diet, High-Fat Mice, Inbred C57BL Disease Models, Animal Infertility, Male / etiology prevention & control metabolism drug therapy Anti-Inflammatory Agents / pharmacology

来  源:   DOI:10.1007/s43032-024-01502-1   PDF(Pubmed)

Abstract:
Obesity is associated with chronic inflammation that affects various organs in the body, including the reproductive system, which is a key factor in male infertility. 1-Deoxynojirimycin (1-DNJ) is a natural alkaloid in mulberry leaves, which has anti-inflammatory capabilities, yet, it\'s effects on obesity-induced inflammation-related male infertility remain unclear. Therefore, this research investigates the underlying mechanism by which 1-DNJ may mitigate fertility impairment in male mice caused by obesity-related inflammation. Male mice with high-fat diet (HFD)-induced obesity were treated with 1-DNJ or metformin for 8 weeks. Metabolic profiles were evaluated by enzyme method. Reproductive capacity was assessed by sperm viability, motility and counts, immunohistochemistry was performed to evaluate the testicular damage caused by obesity and inflammation. The inflammation was assessed by measuring the levels of tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and interleukin 6 (IL-6). The activation of IκB kinase β (IKKβ) and nuclear factor κB (NF-κB) was examined using western blot and immunohistochemistry. HFD induced obesity in mice with obvious lipid metabolism disorder. The obese male mice had a decreased testosterone level, impaired sperm motility, and increased inflammatory factors. 1-DNJ treatment improved the testosterone level in the obese mice, ameliorated the testicular structure damage and improve sperm viability. In addition, 1-DNJ treatment inhibited IKKβ/NF-kB signaling pathway and reduced inflammation in obese mice. 1-DNJ can improve the fertility of obese men by reducing obesity as well as obesity-induced inflammation. These findings provide new insights for 1-DNJ to alleviate inflammation caused by obesity and provide future possibilities for treating male infertility.
摘要:
肥胖与影响身体各种器官的慢性炎症有关,包括生殖系统,这是男性不育的关键因素。1-脱氧野霉素(1-DNJ)是桑叶中的天然生物碱,具有抗炎能力,然而,它对肥胖诱导的炎症相关男性不育的影响尚不清楚。因此,这项研究调查了1-DNJ减轻肥胖相关炎症引起的雄性小鼠生育力损害的潜在机制.用1-DNJ或二甲双胍治疗具有高脂饮食(HFD)诱导的肥胖的雄性小鼠8周。通过酶法评估代谢谱。通过精子活力评估生殖能力,运动性和计数,进行免疫组织化学以评估肥胖和炎症引起的睾丸损伤。通过测量肿瘤坏死因子α(TNFα)的水平来评估炎症。白细胞介素1β(IL-1β),和白细胞介素6(IL-6)。使用蛋白质印迹和免疫组织化学检查IκB激酶β(IKKβ)和核因子κB(NF-κB)的激活。HFD诱导的肥胖小鼠具有明显的脂代谢紊乱。肥胖的雄性小鼠的睾丸激素水平下降,精子运动受损,炎症因子增加。1-DNJ治疗改善了肥胖小鼠的睾酮水平,改善睾丸结构损伤,提高精子活力。此外,1-DNJ治疗抑制IKKβ/NF-kB信号通路并减轻肥胖小鼠的炎症。1-DNJ可以通过减少肥胖以及肥胖引起的炎症来改善肥胖男性的生育能力。这些发现为1-DNJ减轻肥胖引起的炎症提供了新的见解,并为治疗男性不育提供了未来的可能性。
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