Obesity‐related genes are expressed in human Sertoli cells and modulated by energy homeostasis regulating hormones,Journal of Cellular Physiology

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Obesity‐related genes are expressed in human Sertoli cells and modulated by energy homeostasis regulating hormones
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-12-23 , DOI: 10.1002/jcp.30230
Sara C Pereira ₁ , Ana C Martins ₁ , Bruno P Moreira ₁ , Raquel L Bernardino ₁ , Alberto Barros _{2,

3,

4} , Mariana P Monteiro ₅ , Pedro F Oliveira ₆ , Marco G Alves ₁

Affiliation

The strong hormonal dysregulation associated with obesity is responsible for the disruption of several reproductive events. Sertoli cells (SCs) function is dependent on energetic homeostasis and thus, directly associated with energy homeostasis regulating hormones. To further understand the influence of those hormones with SCs function and obesity, we hypothesize that human SCs express obesity‐related genes (ORG; MC4R, GNPDA2, TMEM18, and FTO) and that they respond to energy homeostasis regulating hormones (leptin, ghrelin, and glucagon‐like protein 1 [GLP‐1]) stimuli. To test our hypothesis, SCs were cultured with increasing doses of leptin (0, 5, 25, or 50 ng/ml, for 24 h), ghrelin (0, 20, 100, and 500 pM, for 24 h), and GLP‐1 (10, 1000, or 1 × 105 pM, for 6 h). The presence and abundance of ORG transcripts and proteins in SCs were accessed by polymerase chain reaction techniques, Western blot analysis, and immunofluorescence staining. Our results show that human SCs express MC4R, GNPDA2, TMEM18, and FTO in specific cellular locations. MC4R and FTO expression in human SCs was not responsive to the treatments. However, GNPDA2 and TMEM18 expression increased after exposure to the highest concentration of leptin and ghrelin, respectively. We highlight for the first time that human SCs express ORG and that these are responsive to energy homeostasis hormonal stimuli. GNPDA2 and TMEM18 expression respond in opposite directions according to overall energy status, mediated by energy homeostasis regulating hormones. Leptin and ghrelin control of ORG expression by human SCs can be associated with overweight‐related infertility and subfertility in males.

中文翻译：

肥胖相关基因在人类支持细胞中表达并受能量稳态调节激素的调节

与肥胖相关的强烈荷尔蒙失调是导致几种生殖事件中断的原因。支持细胞 (SC) 的功能依赖于能量稳态，因此与能量稳态调节激素直接相关。为了进一步了解这些激素对 SCs 功能和肥胖的影响，我们假设人类 SCs 表达肥胖相关基因（ORG；MC4R、GNPDA2、TMEM18和FTO) 并且它们对能量稳态调节激素（瘦素、生长素释放肽和胰高血糖素样蛋白 1 [GLP-1]）刺激做出反应。为了验证我们的假设，SCs 用增加剂量的瘦素（0、5、25 或 50 ng/ml，持续 24 小时）、生长素释放肽（0、20、100 和 500 pM，持续 24 小时）和 GLP 进行培养‐1（10、1000 或 1 × 105 pM，6 小时）。通过聚合酶链反应技术、蛋白质印迹分析和免疫荧光染色，获得了 SCs 中 ORG 转录物和蛋白质的存在和丰度。我们的结果表明，人类 SCs 在特定的细胞位置表达 MC4R、GNPDA2、TMEM18 和 FTO。人 SCs 中的MC4R和FTO表达对治疗没有反应。然而，GNPDA2和TMEM18分别暴露于最高浓度的瘦素和生长素释放肽后表达增加。我们首次强调人类 SCs 表达 ORG 并且它们对能量稳态荷尔蒙刺激有反应。GNPDA2和TMEM18表达根据整体能量状态以相反方向响应，由能量稳态调节激素介导。瘦素和生长素释放肽对人类 SCs 的 ORG 表达的控制可能与男性超重相关的不育和不育有关。

更新日期：2020-12-23

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