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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2020

Open Access 01-12-2020 | Insulins | Research

Decreased brain and muscle ARNT-like protein 1 expression mediated the contribution of hyperandrogenism to insulin resistance in polycystic ovary syndrome

Authors: Junyu Zhai, Shang Li, Min Hu, Fangfang Di, Jiansheng Liu, Yanzhi Du

Published in: Reproductive Biology and Endocrinology | Issue 1/2020

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Abstract

Background

The interface between environmental risk factors and genetic factors could contribute to the pathogenesis of hyperandrogenism and insulin resistance in polycystic ovary syndrome (PCOS); however, the underlying complex mechanism remains to be elucidated.

Methods

We used dehydroepiandrosterone (DHEA)-induced PCOS-like rat model to measure circadian clock genes and insulin resistance-related genes. Additionally, we performed in vitro experiments in mature adipocytes to verify the molecular mechanisms.

Results

DHEA-induced PCOS-like rats exhibited insulin resistance and arrhythmic expression of circadian clock genes in the liver and adipose tissues, particularly showing decreased brain and muscle ARNT-like protein 1 (BMAL1) expression. In addition, hyperandrogenism gave rise to negative regulation of BMAL1 expression to nicotinamide phosphoribosyltransferase and sirtuin 1, which further inhibited downstream glucose transporter type 4, leading to insulin resistance in mature adipocytes, which was consistent with our previous results in HepG2 cells.

Conclusions

Decreased BMAL1 expression in the liver and adipose played a potentially novel role in the contribution of hyperandrogenism to insulin resistance, which might be a possible mechanism accounting for the pathogenesis of PCOS.
Appendix
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Metadata
Title
Decreased brain and muscle ARNT-like protein 1 expression mediated the contribution of hyperandrogenism to insulin resistance in polycystic ovary syndrome
Authors
Junyu Zhai
Shang Li
Min Hu
Fangfang Di
Jiansheng Liu
Yanzhi Du
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2020
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-020-00592-1

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