During obesity, excess body weight is not only associated with an increased risk of type 2-diabetes, but also several other pathological processes, such as infertility. Adipose tissue is the largest endocrine organ of the body that produces adipokines, including adiponectin. Adiponectin has been reported to control fertility through the hypothalamic–pituitary–gonadal axis, and folliculogenesis in the ovaries. In this study, we focused on a recent adiponectin-like synthetic agonist called AdipoRon, and its action in human luteinized granulosa cells.

We demonstrated that AdipoRon activated the adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR) signalling pathways in human luteinized granulosa cells. A 25 μM AdipoRon stimulation reduced granulosa cell proliferation by inducing cell cycle arrest in G₁, associated with PTEN and p53 pathway activation. In addition, AdipoRon perturbed cell metabolism by decreasing mitochondrial activity and ATP production. In human luteinized granulosa cells, AdipoRon increased phosphodiesterase activity, leading to a drop in cyclic adenosine monophosphate (cAMP) production, aromatase expression and oestrogens secretion.

In conclusion, AdipoRon impacted folliculogenesis by altering human luteinized granulosa cell function, via steroid production and cell proliferation. This agonist may have applications for improving ovarian function in metabolic disorders or granulosa cancers.

在肥胖期间，超重不仅与 2 型糖尿病风险增加有关，而且与其他几种病理过程有关，例如不孕症。脂肪组织是人体最大的内分泌器官，可产生脂肪因子，包括脂联素。据报道，脂联素通过下丘脑-垂体-性腺轴和卵巢中的卵泡发生来控制生育能力。在这项研究中，我们专注于最近一种名为 AdipoRon 的脂联素样合成激动剂，及其在人类黄体化颗粒细胞中的作用。

我们证明了 AdipoRon 激活了人黄素化颗粒细胞中的单磷酸腺苷激活蛋白激酶 (AMPK) 和过氧化物酶体增殖物激活受体α (PPAR) 信号通路。25 μM AdipoRon 刺激通过诱导与 PTEN 和 p53 通路激活相关的G ₁细胞周期停滞来减少颗粒细胞增殖。此外，AdipoRon 通过降低线粒体活性和 ATP 产生扰乱细胞代谢。在人黄素化颗粒细胞中，AdipoRon 增加磷酸二酯酶活性，导致环磷酸腺苷 (cAMP) 产生、芳香酶表达和雌激素分泌下降。

总之，AdipoRon 通过类固醇产生和细胞增殖改变人类黄体化颗粒细胞功能来影响卵泡生成。这种激动剂可用于改善代谢紊乱或颗粒癌的卵巢功能。