Laboratory of Neurobiology, Department of Zoology, Faculty of Veterinary Medicine and Animal Sciences, Poznan University of Life Sciences, Poznan, Poland.
Molecular and Cell Biology Unit, Poznan University of Medical Sciences, Poznan, Poland.
Epigenetics. 2022 Dec;17(13):2332-2346. doi: 10.1080/15592294.2022.2119120. Epub 2022 Sep 12.
Kisspeptin, produced from the brain and peripheral tissues, may constitute an important link in metabolic regulation in response to external cues, such as diet. The kisspeptin system is well described in the brain. However, its function and regulation in the peripheral tissues, especially in relation to metabolic disease and sex differences, remain to be elucidated. As and , encoding for kisspeptin and kisspeptin receptors, respectively, are altered by overnutrition/fasting and regulated by DNA methylation during puberty and cancer, epigenetic mechanisms in metabolic disorders are highly probable. In the present study, we experimentally induced type 2 diabetes mellitus (DM2) in female Wistar rats using high-fat diet/streptozocin. We analysed expression and DNA methylation of and in the peripheral tissues, using quantitative-reverse-transcription PCR (qRT-PCR) and pyrosequencing. We discovered differential expression of and in peripheral organs in DM2 females, as compared with healthy controls, and the profile differed from patterns reported earlier in males. DM2 in females was linked to the increased mRNA in the liver and increased mRNA in the liver and adipose tissue. However, promoter was hypermethylated in the liver, suggesting gene silencing. Indeed, the increase in DNA methylation of promoter was accompanied by a reduction in Kiss1r protein, implying epigenetic or translational gene repression. Our results deliver novel evidence for tissue-specific differences in and expression in peripheral organs in DM2 females and suggest DNA methylation as a player in regulation of the hepatic kisspeptin system in DM2.
吻肽，由大脑和外周组织产生，可能构成了对外界刺激（如饮食）的代谢调节中的重要环节。吻肽系统在大脑中得到了很好的描述。然而，其在外周组织中的功能和调节，特别是与代谢性疾病和性别差异的关系，仍有待阐明。由于 和 分别编码吻肽和吻肽受体，它们在外周组织中受到营养过剩/禁食的改变，并在青春期和癌症期间受到 DNA 甲基化的调节，因此代谢紊乱中的表观遗传机制是高度可能的。在本研究中，我们使用高脂肪饮食/链脲佐菌素在雌性 Wistar 大鼠中实验性诱导 2 型糖尿病（DM2）。我们使用定量逆转录 PCR（qRT-PCR）和焦磷酸测序分析了外周组织中 和 的表达和 DNA 甲基化。与健康对照组相比，我们发现 DM2 女性外周器官中 和 的表达存在差异，其模式与先前报道的男性不同。DM2 女性与肝脏中 mRNA 的增加和肝脏和脂肪组织中 mRNA 的增加有关。然而，肝脏中的 启动子发生了超甲基化，表明基因沉默。事实上， 启动子 DNA 甲基化的增加伴随着 Kiss1r 蛋白的减少，暗示着表观遗传或翻译基因抑制。我们的研究结果为 DM2 女性外周组织中 和 在特定组织中的表达提供了新的证据，并表明 DNA 甲基化可能是 DM2 中肝脏吻肽系统调节的一个因素。
