Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome

Jun 20, 2022Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Naringenin affects gut bacteria and energy regulation pathways in rats with hormone-induced polycystic ovary syndrome

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Naringenin supplementation significantly reduced body weight and improved hormone levels in a PCOS-like rat model.

At least 15 KEGG pathways related to ovarian function were significantly enriched.
Naringenin improved insulin resistance and mitigated pathological changes in ovarian tissue.
The expression of key proteins involved in metabolism and cell junctions was up-regulated in the colon.
Changes in gut microbiome composition included a decrease in Prevotella and Gemella and an increase in several beneficial bacteria.

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PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism.

METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested.

RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated.

CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.

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Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome

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