Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway.
Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway.
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DOI：
10.1186/s12958-021-00821-1
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发表时间：
2021-09-08
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Mu Y;Dai HG;Luo LB;Yang J
不育是肥胖男性的常见并发症。氧化应激和睾丸细胞凋亡在肥胖导致的精子发生功能障碍中起着关键作用。已有报道，鸢尾素，运动诱导的肌因子，可以减轻氧化损伤和睾丸细胞凋亡在一些疾病，但它在肥胖引起的精子发生功能障碍的作用仍然不清楚。本研究旨在探讨鸢尾素在肥胖所致精子发生障碍中的作用及其机制。采用高脂饲料喂养雄性小鼠24周，建立肥胖小鼠生精障碍模型。为了探索鸢尾素的作用，在开始HFD后16周开始，向小鼠皮下输注重组鸢尾素8周。为了证实AMP活化蛋白激酶α（AMPKα）的作用，使用AMPKα缺陷小鼠。数据显示肥胖患者血清鸢尾素水平降低，与精子计数和前向运动力呈负相关。肥胖小鼠血浆和睾丸中的鸢尾素表达下调。补充鸢尾素可防止HFD诱导的精子发生功能障碍，并增加小鼠的睾酮水平。HFD诱导的氧化应激，内质网（ER）的压力和睾丸细胞凋亡在很大程度上减弱了鸢尾素治疗。从机制上讲，我们确定了鸢尾素激活AMPKα信号通路。在AMPKα缺失的情况下，我们发现鸢尾素对精子发生功能障碍的保护作用在体内和体外均被消除。总之，我们发现鸢尾素通过激活AMPKα信号通路减轻肥胖相关的精子发生功能障碍。基于这些发现，我们推测鸢尾素是一种潜在的治疗肥胖相关的精子发生功能障碍的药物。
Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis. Male mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used. The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro. In conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.
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影响因子：
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