Scholarlink

Background <p>The incidence of reproductive system disorders has been steadily rising in recent years. Moreover, with the rising standard of living, the incidence of metabolic diseases also has been gradually increasing. However, the connection and mechanisms linking reproductive and metabolic diseases are poorly defined.</p> Methods <p>For organelle connectivity analysis, we analyzed mitochondria–endoplasmic reticulum (ER) contacts (MERCs) gene expression using a published single-cell RNA sequencing data. The link between lipid droplets (LDs) and actin cytoskeleton was analyzed by mass-spectrometry-based proteomics. By flow-cytometry-based cell sorting coupled with transmission electron microscopy, we explored the LD-mediated mitochondria–endoplasmic reticulum contacts.</p> Results <p>We found decreased expression of numerous MERC-associated genes, along with a reduction in Leydig cells (LCs), in high-fat diet (HFD) mice. Mechanistically, LDs downregulated the expression of G-actin, leading to the separation of mitochondria from the ER. From a functional perspective, Firsocostat, a lipogenesis enzyme acetyl-CoA carboxylase (ACC) inhibitor, inhibited LD synthesis, which shortened the distance between mitochondria and the ER, improved their functions, and promoted testosterone synthesis. Finally, targeting the LDs offered a promising therapeutic strategy to improve LC function under high-fat conditions, thereby protecting testicular endocrine function.</p> Conclusions <p>HFD leads to reproductive dysfunction by disrupting lipid-droplet-mediated Mito–ER contacts.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

High-fat diet leads to male reproductive dysfunction by disrupting lipid-droplet-mediated organelle crosstalk

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月6日

查看全文
  • Lu Sun,
  • Ao Wang,
  • Yi Zhang,
  • Jinsi Chen,
  • Peng Huang,
  • Kaixuan Zeng,
  • Shuai Huang,
  • Jiayu Huang,
  • Jin Luo,
  • Jiancheng Wang

摘要

Background

The incidence of reproductive system disorders has been steadily rising in recent years. Moreover, with the rising standard of living, the incidence of metabolic diseases also has been gradually increasing. However, the connection and mechanisms linking reproductive and metabolic diseases are poorly defined.

Methods

For organelle connectivity analysis, we analyzed mitochondria–endoplasmic reticulum (ER) contacts (MERCs) gene expression using a published single-cell RNA sequencing data. The link between lipid droplets (LDs) and actin cytoskeleton was analyzed by mass-spectrometry-based proteomics. By flow-cytometry-based cell sorting coupled with transmission electron microscopy, we explored the LD-mediated mitochondria–endoplasmic reticulum contacts.

Results

We found decreased expression of numerous MERC-associated genes, along with a reduction in Leydig cells (LCs), in high-fat diet (HFD) mice. Mechanistically, LDs downregulated the expression of G-actin, leading to the separation of mitochondria from the ER. From a functional perspective, Firsocostat, a lipogenesis enzyme acetyl-CoA carboxylase (ACC) inhibitor, inhibited LD synthesis, which shortened the distance between mitochondria and the ER, improved their functions, and promoted testosterone synthesis. Finally, targeting the LDs offered a promising therapeutic strategy to improve LC function under high-fat conditions, thereby protecting testicular endocrine function.

Conclusions

HFD leads to reproductive dysfunction by disrupting lipid-droplet-mediated Mito–ER contacts.

Graphical abstract