Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type I Diabetic Mice
Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type I Diabetic Mice
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DOI：
10.2147/dmso.s235869
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Chen, Lulu
中科院分区：
文献类型：
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作者：
Li, Yuanxiang;Peng, Miaomiao;Chen, Lulu
目的：高甘油三酯血症被认为是由1型糖尿病(T1 DM)脂肪分解增加所致。然而，有关控制脂肪分解的转录回路的信息在T1 DM中仍然不完整。蛋白精氨酸甲基转移酶4(PRMT4)是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T1 DM中活化的脂解是否受PRMT4的调节。材料和方法：采用重组腺相关病毒在小鼠脂肪组织中过表达PRMT4。小鼠腹腔注射链脲佐菌素(150 mg/kg)建立T1 DM模型。使用商业试剂盒检测血浆胰岛素、甘油三酯、游离脂肪酸(FFAs)水平。结果：高表达PRMT4的T1 DM小鼠血清甘油三酯和游离脂肪酸水平明显升高。我们还观察到PRMT4的过表达导致脂肪垫重量和脂肪细胞大小的减少。此外，与对照组相比，PRMT4过表达的小鼠的脂解相关分子，包括ATGL、HSL和MAGL的表达水平以及HSL的磷酸化水平都有所增加。在体外，PRMT4促进FFAs释放，激活HSL磷酸化，而PRMT4基因敲除则抑制这一过程。结论：PRMT4促进脂肪分解，升高血清甘油三酯。
Purpose: 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.Materials and Methods: 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.Results: 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.Conclusion: PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.