激素敏感性脂肪酶的下调以及胆固醇受体/转运蛋白的失调会影响高脂饮食诱导的少弱精子症小鼠的睾丸脂质稳态和功能。
The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice.
作者信息
Pan Min, Li Jingya, Wang Yujia, Liu Ziao, Li Li, Wang Tongsheng
机构信息
Pharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, No 350 Longzihu Road, Hefei, 230012, China.
Basic Medical College, Hebei Medical University, Shijiazhuang, China.
出版信息
Mol Med. 2025 Aug 4;31(1):274. doi: 10.1186/s10020-025-01327-x.
BACKGROUND
Obesity-induced oligoasthenospermia is associated with testicular lipid metabolism. However, the mechanisms underlying the lipid homeostasis imbalance of obesity-induced oligoasthenospermia are unclear.
METHODS
Male C57BL/6 mice fed a high-fat diet were established for the in vivo model. TM3/TM4 cells were treated with palmitic acid (PA) in vitro. Proteomics analyzed differential proteins in the testis. The Oil red O and Nile red were used to observe lipid droplets (LDs). Filipin staining was used to observe free cholesterol (FC). Hormone-sensitive lipase (HSL), Low-density lipoprotein receptor (LDLr), Scavenger receptor class B type I (SR-BI), and ATP-binding cassette transporter A1 (ABCA1) expressions were analyzed using qRT-PCR, WB, Immunofluorescence, and immunohistochemistry. Testosterone synthesis and Blood-testis barrier (BTB) integrity were evaluated by ELISA, Transmission electron microscope, and WB.
RESULTS
HFD mice exhibited elevated blood lipid, reduced sperm quality, and hormonal imbalances. Meanwhile, testosterone synthesis was impaired, and BTB was damaged in HFD mice. In vivo and in vitro models, LDs deposition was observed, and HSL expression was down-regulated in Leydig and Sertoli cells. However, the expressions of cholesterol uptake receptors and efflux transporters, as well as the levels of FC, in the two cells were inconsistent. In Leydig cells, the expression of cholesterol uptake receptors (LDLr and SR-BI) was upregulated, resulting in increased FC levels. In Sertoli cells, cholesterol efflux transporter (ABCA1) expression was upregulated, and FC levels decreased. Overexpression of HSL ameliorated LDs accumulation and increased testosterone levels.
CONCLUSION
The down-regulation of HSL and dysregulation of cholesterol receptors/transporter may affect lipid homeostasis, thereby damaging testicular function.
背景
肥胖诱导的少弱精子症与睾丸脂质代谢有关。然而，肥胖诱导的少弱精子症脂质稳态失衡的潜在机制尚不清楚。
方法
建立高脂饮食喂养的雄性C57BL/6小鼠体内模型。体外将TM3/TM4细胞用棕榈酸（PA）处理。蛋白质组学分析睾丸中的差异蛋白。用油红O和尼罗红观察脂滴（LDs）。用 Filipin 染色观察游离胆固醇（FC）。采用qRT-PCR、WB、免疫荧光和免疫组化分析激素敏感脂肪酶（HSL）、低密度脂蛋白受体（LDLr）、B 类清道夫受体 I 型（SR-BI）和 ATP 结合盒转运体 A1（ABCA1）的表达。通过 ELISA、透射电子显微镜和 WB 评估睾酮合成和血睾屏障（BTB）完整性。
结果
高脂饮食小鼠血脂升高，精子质量降低，激素失衡。同时，高脂饮食小鼠睾酮合成受损，血睾屏障受损。在体内和体外模型中，均观察到脂滴沉积，且 Leydig 细胞和 Sertoli 细胞中 HSL 表达下调。然而，两种细胞中胆固醇摄取受体和外流转运体的表达以及 FC 水平并不一致。在 Leydig 细胞中，胆固醇摄取受体（LDLr 和 SR-BI）表达上调，导致 FC 水平升高。在 Sertoli 细胞中，胆固醇外流转运体（ABCA1）表达上调，FC 水平降低。HSL 过表达改善了脂滴积累并提高了睾酮水平。
结论
HSL 的下调和胆固醇受体/转运体的失调可能影响脂质稳态，从而损害睾丸功能。
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