长链非编码RNA RLM通过影响AMPK的磷酸化调节HepG2细胞中的脂质沉积

长非编码RNAs（long noncoding RNAs，lncRNAs）是一类长度大于200 nt、不能编码蛋白质的RNA分子，可通过AMPK、胰岛素受体等多种信号通路，调节细胞糖脂代谢。本研究发现，HepG2细胞中一条未报道的长链非编码RNA，命名为lnc-RLM（lnc-regulate lipid metabolism）。通过敲低HepG2细胞中lnc RLM，检测细胞中甘油三脂含量及脂质代谢相关调节因子表达量。结果显示，实验组较对照组甘油三酯含量显著升高（P<0.05）；AMPK磷酸化水平显著下调，脂质合成相关因子SREBP 1c和FAS表达量上调；同时，细胞中乙酰辅酶A羧化酶（ACC）活性较对照组显著上调（P<0.05）。在lnc RLM敲低的HepG2细胞中，利用AMPK激动剂（A-769662）作用细胞24 h，结果显示，降低的AMPK磷酸化水平并不会因AMPK激动剂的作用而显著升高。本研究结果说明，HepG2细胞中敲低lnc-RLM表达量，可通过影响AMPK磷酸化水平，调节HepG2细胞中脂质沉积。这为今后研究AMPK活性调节提供新的可能，也为代谢性疾病的治疗提供了新思路。

Long Non-coding RNA RLM Regulates the Lipid Deposition in HepG2 Cells by Affecting Phosphorylation of AMPK

Long non-coding RNA (lncRNA) is a kind of RNA molecule whose length is more than 200 nt, and does not encode proteins. It can regulate cellular glucose and lipid metabolism through various signaling pathways, such as AMPK and insulin receptor. In this study, we discovered a new lncRNA in HepG2 cells, and named it lnc-RLM. We knocked-down lnc-RLM, and detected the total triglyceride content and the expression of lipid metabolism-related regulatory factors in HepG2 cells. The results showed that the triglyceride content in the knocked-down group was significantly higher than that in the control group (P<0.05). The phosphorylation level of AMPK was significantly down-regulated, and the expression of lipid synthesis-related factors SREBP 1c and FAS were up-regulated. At the same time, the activity of acetyl-CoA carboxylase (ACC) was significantly up-regulated (P<0.05). Furthermore, HepG2 cells with low lnc-RLM expression were treated with AMPK agonists (A-769662) for 24 hours. The results showed that the decreased level of AMPK phosphorylation did not increase significantly by the action of AMPK agonists. Overall, the results suggested that down-regulation of lnc-RLM in HepG2 cells regulated lipid deposition by affecting the phosphorylation of AMPK. It provided a possibility to study the activity of AMPK, and a new idea for metabolic disease therapeutics in the future.