Unveiling ODP4: A breakthrough in PCOS treatment via BAT transplantation.

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-03-14 DOI:10.1016/j.bcp.2025.116871

Fangfang Di, Yan Yan, Lihua Yao, Zhongxiao Zhang, Liwen Song, Jin Qiu, Runjie Zhang

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引用次数: 0

Abstract

Women with polycystic ovary syndrome (PCOS) often face infertility due to endocrine disorders affecting their reproductive, metabolic, and endocrine systems. Although brown adipose tissue (BAT) transplantation has been established to treat polycystic ovaries and hyperandrogenism in PCOS rats, the underlying mechanism is still largely unclear owing to lacking effective clinical treatment. Peptides are believed to significantly contribute to PCOS pathogenesis, however, the specific effects of active peptides released by BAT on PCOS remain largely unexplored. This study sought to identify active peptides secreted in the recipient's BAT and investigate their potential biological functions in PCOS. We validated the impact of BAT transplantation and found that an overexpressed ovary derived peptide 4 (ODP4) in BAT transplantation rats could potentiate the inhibitory effect of dehydroepiandrosterone (DHEA) on granulosa cell (GC) development, yield a stimulatory effect on cell apoptosis and regulate ovulation genes and hormone synthesis. In DHEA-induced PCOS rats, ODP4 restored the estrous cycle and reduced cystic follicles, indicating its potential in PCOS treatment. Furthermore, transcriptomic analysis of KGN cells treated with ODP4 and DHEA showed changes in genes related to mitochondrial activity and oxidative damage. The mechanism results showed that ODP4 enhanced mitochondrial functionality, elevated ATP production, and decreased oxidative damage in KGN cells treatment with DHEA, suggesting its preventive role in mitochondrial malfunction and oxidative damage. These findings reveal unrecognized roles of ODP4 in PCOS pathogenesis. Our study substantiates that the connection between BAT transplantation and PCOS is related to peptidomics. Additionally, ODP4 has prospects for clinical application as an innovative therapeutic PCOS target.

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揭开 ODP4 的面纱：通过 BAT 移植治疗多囊卵巢综合症的突破。

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.