通过LDLR的异构缺失,通过AMPK/Sirt1/PGC-1α通路减少了仓鼠丸胆固醇的毒性
Yun Bai1, Naiheng Hei2, Mingming Gao3
1Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China; Department of Obstetrics and Gynecology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Toxicology letters
|July 17, 2023
概括
高脂肪饮食增加细胞内胆固醇,通过降低AMPK/Sirt1/PGC-1α通路的调节,损害男性生育能力. 低密度脂蛋白受体 (LDLR) 调解这种胆固醇毒性,影响莱迪格细胞和精子生产.
科学领域:
- 生殖生物学 生殖生物学
- 代谢综合征是代谢综合征的一种.
- 分子内分泌学分子内分泌学
背景情况:
- 细胞内胆固醇在男性不孕症中的作用仍然不太清楚.
- 低密度脂蛋白受体 (LDLR) 是细胞胆固醇吸收的关键媒介.
- 研究LDLR对饮食引起的男性不孕症的影响对于理解代谢障碍至关重要.
研究的目的:
- 阐明低密度脂蛋白受体 (LDLR) 在高脂肪饮食引起的男性不孕症中的作用.
- 研究将细胞内胆固醇与丸功能受损联系起来的分子机制.
主要方法:
- 野生型和LDLR异构缺失的雄性金色叙利亚仓鼠被养高脂肪或正常饮食.
- 评估了血生物化学,血清激素,丸组织病理学和AMPK/Sirt1/PGC-1α通路表达.
- 评估了莱迪格细胞 (LCs),塞尔托利细胞和胚胎表皮的参数.
主要成果:
- 高脂肪饮食诱发了脂质失调,莱迪格细胞脂质沉积,丸激素降低,以及野生类型子的塞尔托利细胞数量减少.
- 观察到精子上皮稀薄,丸缩和AMPK/Sirt1/PGC-1α通路的下调.
- LDLR缺乏部分减轻了这些影响,除了高脂血症,表明LDLR依赖的胆固醇毒性.
结论:
- 过度的细胞内胆固醇,由LDLR介导,使莱迪格细胞,塞尔托利细胞和精子的AMPK/Sirt1/PGC-1α通路失活.
- 胆固醇毒性是饮食引起的男性不孕症的一个重要因素.
- 向LDLR可能为代谢相关的男性生殖功能障碍提供治疗策略.
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