Hyperoside mitigates PCOS-associated adipogenesis and insulin resistance by regulating NCOA2-mediated PPAR-γ ubiquitination and degradation

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-01-27 DOI:10.1016/j.lfs.2025.123417

Qi Zhou , Hong Tang , Yongfeng Wang , Yu Hua , Xiaoling Ouyang , Linxia Li

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引用次数: 0

Abstract

Aims

Polycystic ovary syndrome (PCOS) is closely associated with metabolic disorders such as insulin resistance and obesity, but the role of adipogenesis in its pathophysiology remains unclear. This study investigates the role of adipogenesis in PCOS development and evaluates whether hyperoside (HPS), an anti-adipogenic herbal compound, can improve PCOS by inhibiting adipogenesis.

Main methods

A combination of in vivo and in vitro models was used to assess the impact of HPS on ovarian function, insulin resistance, and adipogenesis. PCOS mice were treated with HPS, and their ovarian function and insulin resistance were evaluated. In vitro adipocyte differentiation assays were conducted to examine the effects of HPS on adipogenesis. The target of HPS was analyzed by Surface plasmon resonance. The expression levels of NCOA2 and PPAR-γ ubiquitination and degradation were analyzed using quantitative real-time PCR and Western blotting. Additionally, NCOA2 knockdown experiments were performed to investigate its role in ovarian function, insulin resistance, and adipogenesis in PCOS mice.

Key findings

HPS treatment significantly improved ovarian function, reduced insulin resistance, and suppressed adipogenesis in PCOS mice. Mechanistically, HPS inhibited adipogenesis by reducing NCOA2 expression, thereby preventing PPAR-γ ubiquitination and degradation. Knockdown of NCOA2 further validated its role by improving ovarian function, insulin resistance, and adipogenesis in PCOS models.

Significance

These findings demonstrate that HPS alleviates PCOS by regulating NCOA2-mediated PPAR-γ ubiquitination and degradation, offering new insights into the role of adipogenesis in PCOS pathophysiology.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.