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Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys.长效 MIC-1/GDF15 分子治疗肥胖症：来自小鼠到猴子的证据。
Sci Transl Med. 2017 Oct 18;9(412). doi: 10.1126/scitranslmed.aan8732.
2
Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15.通过脑干限制性 GDF15 受体实现非稳态体重调节。
Nature. 2017 Oct 12;550(7675):255-259. doi: 10.1038/nature24042. Epub 2017 Sep 27.
3
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.GFRAL 是 GDF15 的受体，是配体发挥抗肥胖作用所必需的。
Nat Med. 2017 Oct;23(10):1158-1166. doi: 10.1038/nm.4394. Epub 2017 Aug 28.
4
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.GDF15 的代谢作用是由孤儿受体 GFRAL 介导的。
Nat Med. 2017 Oct;23(10):1215-1219. doi: 10.1038/nm.4393. Epub 2017 Aug 28.
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Correlation of serum anti-Mullerian hormone to follicular follicle stimulating hormone and implantation potential of the ensuing embryos.血清抗苗勒管激素与卵泡刺激素以及后续胚胎着床潜力的相关性。
Clin Chim Acta. 2017 Aug;471:327-333. doi: 10.1016/j.cca.2017.06.023. Epub 2017 Jul 3.
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Proteomic analysis of human follicular fluid in poor ovarian responders during in vitro fertilization.体外受精过程中卵巢反应不良患者卵泡液的蛋白质组学分析
Proteomics. 2017 Mar;17(6). doi: 10.1002/pmic.201600333.
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Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.厌食-恶病质和肥胖症的治疗可能是同一问题的两个方面：TGF-β 超家族细胞因子 MIC-1/GDF15 的作用。
Int J Obes (Lond). 2016 Feb;40(2):193-7. doi: 10.1038/ijo.2015.242. Epub 2015 Dec 1.
8
Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI.人MIC-1/GDF15的血清水平呈昼夜变化模式，未显示出提示饱腹感因子的特征，且与体重指数相关。
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Proteomic analysis of human follicular fluid from fertile women.人卵泡液的蛋白质组学分析。
Clin Proteomics. 2015 Mar 3;12(1):5. doi: 10.1186/s12014-015-9077-6. eCollection 2015.
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Proteomics. Tissue-based map of the human proteome.蛋白质组学。人类蛋白质组组织图谱。
Science. 2015 Jan 23;347(6220):1260419. doi: 10.1126/science.1260419.

生长/分化因子-15 细胞因子在人卵泡液、颗粒细胞和卵母细胞中的存在。

Presence of growth/differentiation factor-15 cytokine in human follicular fluid, granulosa cells, and oocytes.

机构信息

Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic.

International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.

出版信息

J Assist Reprod Genet. 2018 Aug;35(8):1407-1417. doi: 10.1007/s10815-018-1230-5. Epub 2018 Jun 13.

DOI:10.1007/s10815-018-1230-5
PMID:29948426
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6086784/
Abstract

PURPOSE

The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15.

METHODS

This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed.

RESULTS

GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes.

CONCLUSIONS

To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.

摘要

目的

本研究旨在确定生长分化因子 15（GDF-15）是否存在于卵泡液中；评估卵泡液和血清中 GDF-15 水平与研究对象生育状态之间的关系；并检测颗粒细胞、卵母细胞或两者是否产生 GDF-15。

方法

本研究使用了知情同意下从接受体外受精取卵的女性中获得的卵泡液（FF）、血清和卵母细胞；还使用了因早产死亡的新生儿卵巢。在取卵时采集 FF 和血液，通过 ELISA 和 Western blot 测定 GDF-15 的水平和形式。分析 FF 和血清中 GDF-15 的浓度、卵巢组织中的表达以及颗粒细胞的分泌情况。

结果

ELISA 测定 FF 中 GDF-15 的浓度范围为 35 至 572ng/ml。Western blot 分析显示 FF 中仅存在 GDF-15 前体二聚体。正常健康和癌性颗粒细胞均将 GDF-15 分泌到培养基中。在免疫染色的新生儿卵巢中，初级卵母细胞显示细胞质 GDF-15 阳性，并且在完全成熟的人类卵母细胞中也观察到其表达。

结论

据我们所知，这是首次在卵泡液中发现细胞因子 GDF-15 的存在。其浓度与供体/患者的生育状态无关。我们的数据还表明，GDF-15 在正常健康和癌性颗粒细胞以及卵母细胞中均有表达和诱导。