Fibroblast growth factor 21 coordinates adiponectin to mediate the beneficial effects of low-protein diet on primordial follicle reserve
Fibroblast growth factor 21 coordinates adiponectin to mediate the beneficial effects of low-protein diet on primordial follicle reserve
复制标题
成纤维细胞生长因子 21 协调脂联素介导低蛋白饮食对原始卵泡储备的有益影响
DOI：
10.1016/j.ebiom.2019.02.020
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Wu, De
中科院分区：
文献类型：
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作者：
Zhuo, Yong;Hua, Lun;Wu, De
背景：全球人均蛋白质消费量正在上升，而不孕症的发病率也在上升。然而，蛋白质摄入量与生殖健康之间的明确关系尚未得到证实。静止原始卵泡的激活是卵泡发生的第一步，必须严格控制其激活，以防止卵巢卵泡储备的过早耗尽。方法：在小鼠体内检测野生型或肝脏特异性消融成纤维细胞生长因子21（FGF 21）的原始卵泡储备，进行限制或过量蛋白饮食或口服灌胃试验。小鼠卵巢器官培养物被用来检查原始卵泡activation.Findings的代谢产物或代谢激素的直接作用：小鼠原始卵泡激活，减少限制蛋白质摄入量，并加速过量的蛋白质摄入量，在卵巢mTORC 1信号依赖的方式。此外，限制或过量的蛋白质摄入导致增加或减少卵母细胞数量和生育能力在老年人，分别。肝脏特异性消融FGF 21，导致循环FGF 21减少87%，消除了低蛋白摄入对原始卵泡池的保护作用。有趣的是，FGF 21对原始卵泡的激活没有直接影响，而是需要脂肪因子脂联素。此外，口服脂联素受体激动剂AdipoRon可阻止过量蛋白质摄入对原始卵泡激活的过度激活效应。解释：膳食蛋白质消耗控制卵巢原始卵泡储备和生育，这需要FGF 21和脂联素的协调作用。基金：国家自然科学基金（31772616）。(c)2019年，任作家。由Elsevier B. V.发布。这是CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background: Global consumption of protein per capita is rising, while rates of infertility are increasing. However, a clear relationship between protein intake and reproductive health has not been demonstrated. The activation of the quiescent primordial follicles is the first step of folliculogenesis, and their activation must be tightly controlled to prevent premature exhaustion of the ovarian follicular reserve.Methods: The primordial follicle reserve of wild-type or liver-specific ablation of fibroblast growth factor 21 (FGF21) in mice, subjected to limited or excessive protein diets or oral gavage test, were detected in vivo. Mouse ovary organ cultures were used to examine the direct role of metabolites or metabolic hormones on primordial follicle activation.Findings: Mouse primordial follicle activation, was reduced by restricted protein intake and was accelerated by excessive protein intake, in an ovarian mTORC1 signaling-dependent manner. Furthermore, restricted or excessive protein intake resulted in an augmentation or decline of oocyte number and fertility at older age, respectively. Liver-specific ablation of FGF21, which resulted in a reduction of 87% in circulating FGF21, abrogated the preserving effect of low-protein intake on primordial follicle pool. Interestingly, FGF21 had no direct effect on the activation of primordial follicles, but instead required an adipokine adiponectin. Moreover, AdipoRon, an oral adiponectin receptor agonist, prevented the over-activation effect of excessive protein intake on primordial follicle activation.Interpretation: Dietary protein consumption controlled ovarian primordial follicle reserve and fertility, which required coordination between FGF21 and adiponectin.Fund: Natural Science Foundation of China (Grant 31772616). (c) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).