Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing, China.
Mol Reprod Dev. 2020 Feb;87(2):241-250. doi: 10.1002/mrd.23321. Epub 2020 Feb 6.
Overweight and obese men face numerous health problems, including type 2 diabetes, subfertility, and even infertility. However, few studies have focused on the effects of nutritional status and obesity-related regulatory signals on fertility deficiency. Our previous observations have shown that the elevation of plasma 5'-adenosine monophosphate (5'-AMP) and the accumulation of adenosine in liver and muscle of obese diabetic db/db mice are related to insulin resistance. Here, we found that adenosine accumulation in testis is a common marker of both genetic obesity and high-fat-diet induced obese mice. An messenger RNA sequencing analysis indicated that 78 upregulated genes and 155 downregulated genes in the testis of 5'-AMP-treated mice overlapped with the same genes in the testis of ob/ob mice, and these genes belonged to the clusters of steroid metabolic process and regulation of hormone levels, respectively. Serum testosterone was reduced in ob/ob and 5'-AMP-treated mice. Metabolomic analysis based on H nuclear magnetic resonance showed that the testicular metabolic profiles of ob/ob mice were similar to those of 5'-AMP treated mice. Exogenous 5'-AMP inhibited the phosphorylation of AKT and mammalian target of rapamycin signal transduction and reduced the proliferating cell nuclear antigen expressions in testes. Our results suggest that the accumulation of adenosine causes metabolic disorders in testes and associates lower testosterone level in obese mice.
超重和肥胖的男性面临许多健康问题，包括 2 型糖尿病、生育能力低下甚至不育。然而，很少有研究关注营养状况和肥胖相关调节信号对生育能力不足的影响。我们之前的观察结果表明，肥胖糖尿病 db/db 小鼠血浆 5'-单磷酸腺苷（5'-AMP）升高和肝、肌肉中腺苷积累与胰岛素抵抗有关。在这里，我们发现睾丸中腺苷的积累是遗传肥胖和高脂肪饮食诱导肥胖小鼠的共同标志。信使 RNA 测序分析表明，5'-AMP 处理小鼠睾丸中 78 个上调基因和 155 个下调基因与 ob/ob 小鼠睾丸中的相同基因重叠，这些基因分别属于类固醇代谢过程和激素水平调节簇。ob/ob 和 5'-AMP 处理小鼠的血清睾酮降低。基于 H 核磁共振的代谢组学分析表明，ob/ob 小鼠的睾丸代谢图谱与 5'-AMP 处理小鼠的相似。外源性 5'-AMP 抑制 AKT 和哺乳动物雷帕霉素靶蛋白信号转导的磷酸化，降低睾丸中增殖细胞核抗原的表达。我们的结果表明，腺苷的积累导致肥胖小鼠睾丸代谢紊乱，并与较低的睾丸酮水平相关。
