Able Ashley A, Richard Allison J, Stephens Jacqueline M
Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Biology (Basel). 2023 Apr 30;12(5):674. doi: 10.3390/biology12050674.
Impaired adipocyte function contributes to systemic metabolic dysregulation, and altered fat mass or function increases the risk of Type 2 diabetes. EHMTs 1 and 2 (euchromatic histone lysine methyltransferases 1 and 2), also known as the G9a-like protein (GLP) and G9a, respectively, catalyze the mono- and di-methylation of histone 3 lysine 9 (H3K9) and also methylate nonhistone substrates; in addition, they can act as transcriptional coactivators independent of their methyltransferase activity. These enzymes are known to contribute to adipocyte development and function, and in vivo data indicate a role for G9a and GLP in metabolic disease states; however, the mechanisms involved in the cell-autonomous functions of G9a and GLP in adipocytes are largely unknown. Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine typically induced in adipose tissue in conditions of insulin resistance and Type 2 diabetes. Using an siRNA approach, we have determined that the loss of G9a and GLP enhances TNFα-induced lipolysis and inflammatory gene expression in adipocytes. Furthermore, we show that G9a and GLP are present in a protein complex with nuclear factor kappa B (NF-κB) in TNFα-treated adipocytes. These novel observations provide mechanistic insights into the association between adipocyte G9a and GLP expression and systemic metabolic health.
脂肪细胞功能受损会导致全身代谢失调，而脂肪量或功能的改变会增加2型糖尿病的风险。EHMT1和EHMT2（常染色质组蛋白赖氨酸甲基转移酶1和2），也分别被称为G9a样蛋白（GLP）和G9a，催化组蛋白3赖氨酸9（H3K9）的单甲基化和二甲基化，并且还使非组蛋白底物甲基化；此外，它们可以作为独立于其甲基转移酶活性的转录共激活因子。已知这些酶有助于脂肪细胞的发育和功能，体内数据表明G9a和GLP在代谢疾病状态中发挥作用；然而，G9a和GLP在脂肪细胞中细胞自主功能所涉及的机制在很大程度上尚不清楚。肿瘤坏死因子α（TNFα）是一种促炎细胞因子，通常在胰岛素抵抗和2型糖尿病的情况下在脂肪组织中诱导产生。使用RNA干扰方法，我们已经确定G9a和GLP的缺失会增强TNFα诱导的脂肪细胞中的脂肪分解和炎症基因表达。此外，我们表明在TNFα处理的脂肪细胞中，G9a和GLP与核因子κB（NF-κB）存在于一个蛋白复合物中。这些新发现为脂肪细胞G9a和GLP表达与全身代谢健康之间的关联提供了机制上的见解。
