The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice.
Min Pan, Jingya Li, Yujia Wang, Ziao Liu, Li Li, Tongsheng Wang
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引用次数: 0
Abstract
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.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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