CONACYT-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán.; Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico.
Laboratorio Translacional de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-A X Av, Itzaes Costado Sur "Parque de la Paz", Col. Centro, Mérida 97000, Yucatán, Mexico.
Int J Mol Sci. 2019 Aug 12;20(16):3918. doi: 10.3390/ijms20163918.
Obesity is a rising public health problem that contributes to the development of several metabolic diseases and cancer. Adipocyte precursors outside of adipose depots that expand due to overweight and obesity may have a negative impact on human health. Determining how progenitor cells acquire a preadipocyte commitment and become mature adipocytes remains a significant challenge. Over the past several years, we have learned that the establishment of cellular identity is widely influenced by changes in histone marks, which in turn modulate chromatin structure. In this regard, histone lysine demethylases (KDMs) are now emerging as key players that shape chromatin through their ability to demethylate almost all major histone methylation sites. Recent research has shown that KDMs orchestrate the chromatin landscape, which mediates the activation of adipocyte-specific genes. In addition, KDMs have functions in addition to their enzymatic activity, which are beginning to be revealed, and their dysregulation seems to be related to the development of metabolic disorders. In this review, we highlight the biological functions of KDMs that contribute to the establishment of a permissive or repressive chromatin environment during the mesenchymal stem cell transition into adipocytes. Understanding how KDMs regulate adipogenesis might prompt the development of new strategies for fighting obesity-related diseases.
肥胖是一个日益严重的公共卫生问题,它会导致多种代谢性疾病和癌症的发生。由于超重和肥胖而扩张的脂肪组织外的脂肪细胞前体可能对人类健康产生负面影响。确定祖细胞如何获得前脂肪细胞的承诺并成为成熟的脂肪细胞仍然是一个巨大的挑战。在过去的几年中,我们了解到细胞身份的建立受到组蛋白标记变化的广泛影响,这些变化又反过来调节染色质结构。在这方面,组蛋白赖氨酸去甲基酶(KDMs)现在作为关键的参与者出现,它们通过能够去甲基化几乎所有主要的组蛋白甲基化位点来塑造染色质。最近的研究表明,KDMs 协调染色质景观,介导脂肪细胞特异性基因的激活。此外,KDMs 除了具有酶活性外还有其他功能,这些功能开始被揭示出来,它们的失调似乎与代谢紊乱的发展有关。在这篇综述中,我们强调了 KDMs 的生物学功能,这些功能有助于间充质干细胞向脂肪细胞转化过程中建立允许或抑制染色质环境。了解 KDMs 如何调节脂肪生成可能会促使人们开发出治疗肥胖相关疾病的新策略。