The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice
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 viv...
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2025-08-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01327-x |
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| author | Min Pan Jingya Li Yujia Wang Ziao Liu Li Li Tongsheng Wang |
| author_facet | Min Pan Jingya Li Yujia Wang Ziao Liu Li Li Tongsheng Wang |
| author_sort | Min Pan |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj-art-4cf274dbd1694089b2b352d14e7ad1642025-08-20T03:45:52ZengBMCMolecular Medicine1528-36582025-08-0131111810.1186/s10020-025-01327-xThe downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia miceMin Pan0Jingya Li1Yujia Wang2Ziao Liu3Li Li4Tongsheng Wang5Pharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicinePharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineBasic Medical College, Hebei Medical UniversityPharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicinePharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicinePharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese MedicineAbstract 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.https://doi.org/10.1186/s10020-025-01327-xObesity with oligoasthenospermiaLipid homeostasisHSLCholesterol receptorsCholesterol transporterTesticular function |
| spellingShingle | Min Pan Jingya Li Yujia Wang Ziao Liu Li Li Tongsheng Wang The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice Molecular Medicine Obesity with oligoasthenospermia Lipid homeostasis HSL Cholesterol receptors Cholesterol transporter Testicular function |
| title | The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice |
| title_full | The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice |
| title_fullStr | The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice |
| title_full_unstemmed | The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice |
| title_short | The downregulation of hormone-sensitive lipase and dysregulation of cholesterol receptors/transporter affect testicular lipid homeostasis and function in HFD-induced oligoasthenospermia mice |
| title_sort | downregulation of hormone sensitive lipase and dysregulation of cholesterol receptors transporter affect testicular lipid homeostasis and function in hfd induced oligoasthenospermia mice |
| topic | Obesity with oligoasthenospermia Lipid homeostasis HSL Cholesterol receptors Cholesterol transporter Testicular function |
| url | https://doi.org/10.1186/s10020-025-01327-x |
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