Li Yuanxiang, Peng Miaomiao, Zeng Tianshu, Zheng Juan, Liao Yunfei, Zhang Hao, Yang Songtao, Chen Lulu
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People's Republic of China.
Diabetes Metab Syndr Obes. 2020 Feb 26;13:535-544. doi: 10.2147/DMSO.S235869. eCollection 2020.
Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4.
Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis.
Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes.
PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.
高甘油三酯血症被认为是由1型糖尿病（T1DM）中脂解增加所驱动。然而，在T1DM中，关于调控脂解的转录调控网络的信息仍不完整。蛋白质精氨酸甲基转移酶4（PRMT4）作为一种转录共激活因子，可促进自噬，并可能在脂解中发挥重要作用。我们想知道T1DM中激活的脂解是否受PRMT4调控。
采用重组腺相关病毒在小鼠脂肪组织中过表达PRMT4。将链脲佐菌素（150mg/kg）腹腔注射到小鼠体内以诱导T1DM。使用商用检测试剂盒测定血浆胰岛素、甘油三酯、游离脂肪酸（FFA）水平。应用分化的脂肪细胞来验证PRMT4对脂解的调控作用。
在过表达PRMT4的T1DM小鼠中观察到血清甘油三酯和FFA升高。我们还观察到PRMT4过表达导致脂肪垫重量和脂肪细胞大小减小。此外，与对照小鼠相比，过表达PRMT4的小鼠中脂解相关分子（包括ATGL、HSL和MAGL）的表达水平以及HSL磷酸化水平均升高。在体外，PRMT4促进FFA释放并激活HSL磷酸化，而敲低PRMT4则抑制这些过程。
PRMT4在T1DM中促进脂解并增加血清甘油三酯水平。
