Centro de Investigaciones Endocrinológicas, "Dr César Bergadá", CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Argentina.
Centro de Investigaciones Endocrinológicas, "Dr César Bergadá", CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Argentina.
Mol Cell Endocrinol. 2025 Jan 1;595:112403. doi: 10.1016/j.mce.2024.112403. Epub 2024 Oct 28.
Sertoli cells (SCs) are essential for appropriate spermatogenesis. From a metabolic standpoint, they catabolize glucose and provide germ cells with lactate, which is their main energy source. SCs also oxidize fatty acids (FAs), which are stored as triacylglycerides (TAGs) within lipid droplets (LDs), to fulfill their own energy requirements. On the other hand, it has been demonstrated that FSH regulates some of SCs functions, but little is known about its effect on lipid metabolism. In the present study, we aimed to analyze FSH-mediated regulation of (1) lipid storage in LDs and (2) the expression of genes involved in FAs activation and TAG synthesis and storage in SCs. SCs obtained from 20-day-old rats were cultured for different incubation periods with FSH (100 ng/ml). It was observed that FSH increased LD content and TAG levels in SCs. There were also increments in the expression of Plin1, Fabp5, Acsl1, Acsl4, Gpat3, and Dgat1, which suggests that these proteins may mediate the increase in TAGs and LDs elicited by FSH. Regarding the signaling involved in FSH actions, it was observed that dbcAMP increased LD, and H89, a PKA inhibitor, inhibited FSH stimulus. Also, dbcAMP increased Plin2, Fabp5, Acsl1, Acsl4, and Dgat1 mRNA levels, confirming a role of the cAMP/PKA pathway in the regulation of lipid storage in SCs. Altogether, these results suggest that FSH, via the cAMP/PKA pathway, regulates lipid storage in SCs ensuring the availability of substrates to satisfy their energy requirements.
支持细胞(SCs)对适当的精子发生至关重要。从代谢的角度来看,它们分解葡萄糖并为生殖细胞提供乳酸,这是它们的主要能量来源。SCs 还氧化脂肪酸(FAs),这些脂肪酸被储存为三酰基甘油(TAGs)在脂质滴(LDs)中,以满足它们自己的能量需求。另一方面,已经证明 FSH 调节一些SCs 的功能,但对其对脂质代谢的影响知之甚少。在本研究中,我们旨在分析 FSH 介导的(1)LD 中的脂质储存和(2)参与 FAs 激活和 TAG 合成和储存的基因表达的调节。从 20 天大的大鼠中获得的SCs 培养不同的孵育时间与 FSH(100 ng/ml)。结果表明,FSH 增加了 SCs 中的 LD 含量和 TAG 水平。Plin1、Fabp5、Acsl1、Acsl4、Gpat3 和 Dgat1 的表达也增加,这表明这些蛋白可能介导 FSH 引起的 TAG 和 LDs 的增加。关于涉及 FSH 作用的信号,观察到 dbcAMP 增加 LD,PKA 抑制剂 H89 抑制 FSH 刺激。此外,dbcAMP 增加了 Plin2、Fabp5、Acsl1、Acsl4 和 Dgat1 mRNA 水平,证实了 cAMP/PKA 途径在调节 SCs 中的脂质储存中的作用。总之,这些结果表明,FSH 通过 cAMP/PKA 途径调节 SCs 中的脂质储存,以确保满足其能量需求的底物的可用性。