College of Animal Science and Technology, Guangxi University, Nanning 530004, China.
Int J Mol Sci. 2022 Jul 22;23(15):8066. doi: 10.3390/ijms23158066.
Gonadotropin-inhibitory hormone (GnIH) is a reproductive inhibitor and an endogenous orexigenic neuropeptide that may be involved in energy homeostasis and reproduction. However, whether GnIH is a molecular signal link of metabolism and the reproductive system, and thus, regulates reproductive activity as a function of the energy state, is still unknown. In the present study, we investigated the involvement of GnIH in glycolipid metabolism and reproduction in vivo, and in the coupling between these two processes in the testis level. Our results showed that chronic intraperitoneal injection of GnIH into male mice not only increased food intake and altered meal microstructure but also significantly elevated body mass due to the increased mass of liver and epididymal white adipose tissue (eWAT), despite the loss of testicular weight. Furthermore, chronic intraperitoneal administration of GnIH to male mice resulted in obesity-related glycolipid metabolic derangements, showing hyperlipidemia, hyperglycemia, glucose intolerance, and insulin resistance through changes in the expression of glucose and lipid metabolism-related genes in the pancreas and eWAT, respectively. Interestingly, the expression of GnIH and GPR147 was markedly increased in the testis of mice under conditions of energy imbalance, such as fasting, acute hypoglycemia, and hyperglycemia. In addition, chronic GnIH injection markedly inhibited glucose and lipid metabolism of mice testis while significantly decreasing testosterone synthesis and sperm quality, inducing hypogonadism. These observations indicated that orexigenic GnIH triggers hyperphagia-induced obesity-related metabolic derangements and hypogonadism in male mice, suggesting that GnIH is an emerging candidate for coupling metabolism and fertility by involvement in obesity and metabolic disorder-induced reproductive dysfunction of the testes.
促性腺激素抑制激素 (GnIH) 是一种生殖抑制剂和内源性摄食促进神经肽，可能参与能量平衡和生殖。然而，GnIH 是否是代谢和生殖系统的分子信号联系，从而作为能量状态的功能调节生殖活动，目前尚不清楚。在本研究中，我们研究了 GnIH 在体内糖脂代谢和生殖中的作用，以及在睾丸水平上这两个过程之间的耦合。我们的结果表明，慢性腹腔内注射 GnIH 不仅增加了雄性小鼠的食物摄入量和改变了进食的微观结构，而且由于肝脏和附睾白色脂肪组织（eWAT）质量的增加，还显著增加了体重，尽管睾丸重量减轻。此外，慢性腹腔内给予 GnIH 导致肥胖相关的糖脂代谢紊乱，通过改变胰腺和 eWAT 中与葡萄糖和脂质代谢相关的基因表达，表现为高脂血症、高血糖、葡萄糖耐量受损和胰岛素抵抗。有趣的是，在能量失衡的情况下，如禁食、急性低血糖和高血糖，GnIH 和 GPR147 的表达在小鼠睾丸中明显增加。此外，慢性 GnIH 注射显著抑制了小鼠睾丸的葡萄糖和脂质代谢，同时显著降低了睾丸激素的合成和精子质量，导致性腺功能减退。这些观察结果表明，摄食促进性 GnIH 引发雄性小鼠的暴食诱导性肥胖相关代谢紊乱和性腺功能减退，表明 GnIH 是通过参与肥胖和代谢紊乱诱导的睾丸生殖功能障碍来连接代谢和生育的新兴候选者。
