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

IF 5.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-03-01 Epub 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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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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金丝桃苷通过调节ncoa2介导的PPAR-γ泛素化和降解,减轻pcos相关的脂肪形成和胰岛素抵抗。
目的:多囊卵巢综合征(PCOS)与胰岛素抵抗和肥胖等代谢紊乱密切相关,但脂肪生成在其病理生理中的作用尚不清楚。本研究探讨脂肪形成在多囊卵巢综合征(PCOS)发生中的作用,并评估抗脂肪形成的草药化合物金丝桃苷(HPS)是否通过抑制脂肪形成来改善多囊卵巢综合征(PCOS)。主要方法:采用体内和体外相结合的方法,评估HPS对卵巢功能、胰岛素抵抗和脂肪生成的影响。用HPS治疗PCOS小鼠,观察其卵巢功能和胰岛素抵抗。体外脂肪细胞分化实验研究了HPS对脂肪形成的影响。利用表面等离激元共振对HPS靶进行了分析。采用实时荧光定量PCR和Western blotting分析NCOA2和PPAR-γ泛素化和降解的表达水平。此外,我们还进行了NCOA2敲低实验,以研究其在PCOS小鼠卵巢功能、胰岛素抵抗和脂肪生成中的作用。主要发现:HPS治疗显著改善PCOS小鼠卵巢功能,降低胰岛素抵抗,抑制脂肪生成。从机制上讲,HPS通过降低NCOA2的表达来抑制脂肪形成,从而阻止PPAR-γ泛素化和降解。在PCOS模型中,敲低NCOA2进一步证实了其改善卵巢功能、胰岛素抵抗和脂肪生成的作用。意义:这些发现表明HPS通过调节ncoa2介导的PPAR-γ泛素化和降解来缓解PCOS,为脂肪形成在PCOS病理生理中的作用提供了新的认识。
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来源期刊
Life sciences
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.
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