LncNONMMUG027912 alleviates lipid accumulation through AMPKα/mTOR/SREBP1C axis in nonalcoholic fatty liver.

Various metabolic diseases are closely related to lipid metabolism disorders, but the regulatory effect of long noncoding RNAs (lncRNAs) on the function of lipids has been poorly elucidated. Previous our work has found that lncNONMMUG027912 (abbreviated as lnc027912) involved in cholesterol metabolism. Here, we further explored the novel function of lipid metabolism-associated lnc027912. We found that upregulated lnc027912 in AML12 cells treated with oleic acid (OA) and palmitic acid (PA) showed a significant decrease in lipid accumulation, triglyceride (TG) levels, and lipid biosynthesis genes. In terms of regulatory mechanisms, lnc027912 increased the expression of p-AMPKα, inhibited p-mTOR levels, decreased the expression of SREBP1C in nuclei, decreased the promoter activity of SREBP1C, and inhibited the expression of lipid synthesis genes. Most importantly, lnc027912 could reduce lipid accumulation and liver inflammation through AMPKα/mTOR signal axis in nonalcoholic fatty liver disease (NAFLD) mice model. Altogether, our study revealed a novel molecular mechanism of lnc027912 in lipid metabolism through the AMPKα/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new treatment target for lipid disorder diseases (such as NAFLD).