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  3. Gut microbiota disorder induces liver dysfunction in polycystic ovary syndrome rats' model by regulating metabolite rosmarinic acid

Gut microbiota disorder induces liver dysfunction in polycystic ovary syndrome rats' model by regulating metabolite rosmarinic acid

  • Life Sci. 2023 Jul 7;121912. doi: 10.1016/j.lfs.2023.121912.
Tingting Zhang 1,  Huimin Gao 1,  Yali Fan 1,  Shuya Chen 1,  Yingying Li 1,  Ruixia Liu 1,  Tianhe Li 2,  Chenghong Yin 3
Affiliations

Affiliations

  • 1 Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
  • 2 Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China. Electronic address: lth_felicity@ccmu.edu.cn.
  • 3 Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China. Electronic address: yinchh@ccmu.edu.cn.
PMID: 37423380 DOI: 10.1016/j.lfs.2023.121912
Abstract

Aims: The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS.

Materials and methods: PCOS rat models were established by treating Sprague Dawley (SD) rats with DHEA (an androgen, 60 mg/kg) and LET (a nonsteroidal aromatase inhibitor, 1 mg/kg) for 90 days. Hematoxylin and eosin staining (H&E), Western blotting, and radioimmunoassay were employed to test ovarian and liver functions. Gut microbiome and serum metabolites were assessed using 16S rRNA amplicon Sequencing and non-targeted metabolomics, respectively. The association between gut microbiota and serum metabolites was examined using Spearman analysis. Finally, using HepG2 cells to investigate the function of the serum metabolite rosmarinic acid (RA).

Key findings: Both Dehydroepiandrosterone (DHEA) and letrozole (LET) treatments induced a PCOS phenotype and liver dysfunction. However, LET resulted in more severe lipid accumulation and liver cell Apoptosis than DHEA. 16S rRNA Sequencing and non-targeted metabolomics analysis revealed significant differences in beta diversity and serum metabolite profiles among the three groups. Furthermore, among the significantly changed metabolites, RA was found to have a significant correlation with the levels of serum aspartate transaminase (AST) and Lactate Dehydrogenase (LDH) and could promote HepG2 cell Apoptosis.

Significance: Restoring gut microbiota, altering serum metabolites and/or decreasing RA may provide a new insight to treat this complication.

Keywords

Gut microbiota; Liver dysfunction; Metabolites; Polycystic ovary syndrome.

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