Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non‐alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long non‐coding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM‐NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM‐NAFLD model was established by high‐energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG‐treated hepatocytes and livers from DM‐NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG‐induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element‐binding proteins 1‐c [SREBP‐1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose‐6‐phosphatase [G6Pase]). Further in vivo assays showed that lentivirus‐mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP‐1c and FAS in DM‐NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM‐NAFLD.

中文翻译：

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敲低长链非编码RNA Gm10804可抑制患有非酒精性脂肪肝疾病的糖尿病患者的肝糖和脂质代谢异常

葡萄糖和脂质代谢失调是与糖尿病（DM）和非酒精性脂肪肝疾病（NAFLD）相关的主要潜在表现。这项研究旨在探讨新型长非编码RNA（lncRNA）Gm10804在调节DM合并NAFLD（DM-NAFLD）的肝糖和脂质代谢中的作用。暴露于高葡萄糖（HG）的小鼠原代肝细胞被用作细胞模型。通过高能喂养与腹膜内注射链脲佐菌素建立了小鼠DM-NAFLD模型。结果表明，在DM-NAFLD小鼠的HG处理的肝细胞和肝脏中，Gm10804表达上调。体外肝细胞的结果表明，Gm10804的过度表达加剧了，而Gm10804的沉默消除了HG诱导的细胞内甘油三酸酯（TG）含量的增加，脂质积累和肝脂肪蛋白（固醇调节元件结合蛋白1-c [SREBP-1c]和脂肪酸合酶[FAS]）和糖异生酶（磷酸烯醇丙酮酸羧激酶[PEPCK]和葡萄糖-6-磷酸酶[G6Pase]）的表达）。进一步的体内分析表明，慢病毒介导的Gm10804肝敲除可减轻DM-NAFLD小鼠的肝脂肪变性和脂质蓄积，并降低肝PEPCK，G6Pase，SREBP-1c和FAS的表达。总之，Gm10804敲低可通过改善DM-NAFLD中的肝糖异常和脂质代谢紊乱来减轻肝脂质蓄积。