Effect of globin peptide on female fertility in aging granulosa cell-specific Nrg1 knockout mice

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-03-12 DOI:10.1262/jrd.2023-076

Takashi UMEHARA, Marino OGASAHARA, D.M.V. Supun PREMARATHNE, Yuka SASAKAWA, Yasuo SUMIDA, Masayuki SHIMADA

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Abstract

Ovarian fibrosis contributes to age-related ovarian dysfunction. In our previous study, we observed ovarian fibrosis in both obese and aging mice with intracellular lipid droplets in the fibrotic ovaries. Although the importance of mitochondria in ovarian fibrosis has been recognized in pharmacological studies, their role in lipid metabolism remains unclear. Globin peptide (GP), derived from hemoglobin, enhances lipid metabolism in obese mice. This study aimed to elucidate the importance of lipid metabolism in ovarian fibrosis by using GP. Treatment of ovarian stromal cells with GP increased mitochondrial oxygen consumption during β-oxidation. Lipid accumulation was also observed in the ovaries of granulosa cell-specific Nrg1 knockout mice (gcNrg1KO), and the administration of GP to gcNrg1KO mice for two months reduced ovarian lipid accumulation and fibrosis in addition to restoring the estrous cycle. GP holds promise for mitigating lipid-related ovarian issues and provides a novel approach to safeguarding ovarian health by regulating fibrosis via lipid pathways.

Graphical Abstract Fullsize Image

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球蛋白肽对衰老颗粒细胞特异性 Nrg1 基因敲除小鼠雌性生育能力的影响

卵巢纤维化是与年龄有关的卵巢功能障碍的原因之一。在我们之前的研究中，我们观察到肥胖小鼠和衰老小鼠的卵巢纤维化，纤维化卵巢中存在细胞内脂滴。虽然线粒体在卵巢纤维化中的重要性已在药理学研究中得到认可，但它们在脂质代谢中的作用仍不清楚。从血红蛋白中提取的球蛋白肽（GP）能促进肥胖小鼠的脂质代谢。本研究旨在利用 GP 阐明脂质代谢在卵巢纤维化中的重要性。用GP处理卵巢基质细胞可增加β氧化过程中线粒体的耗氧量。在颗粒细胞特异性 Nrg1 基因敲除小鼠（gcNrg1KO）的卵巢中也观察到脂质积累，给 gcNrg1KO 小鼠服用两个月的 GP 可减少卵巢脂质积累和纤维化，还能恢复发情周期。GP有望缓解与脂质相关的卵巢问题，并通过脂质途径调节纤维化，为保障卵巢健康提供了一种新方法。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.