Abstract
BackgroundOur study aims to investigate the mechanisms of lncRNA Gm12664–001 improved hepatic lipid accumulation-initiated NAFLD via regulating miR-295-5p and CAV1 in AML12 cells.MethodsThe animals were divided into normal control (NC) group and high fat diet (HFD) group (20 mice per group) for 8w. The steatotic liver was measured by hematoxylin eosin (HE) staining and kits. We performed systematical analyses on hepatic expression profiles of long noncoding RNAs (lncRNAs) and microRNAs in a high-fat diet (HFD)-induced steatotic animal model. The expression profile of targets was confirmed by bioinformatics analysis, luciferase assay, RT-PCR and western blot in AML12 cells.ResultsHFD treatment markedly observed hepatic fatty degeneration with primarily fat vacuoles, and increased TG level compared with control. According to microarray data, we found that transfection of Gm12664–001 siRNA (siRNA-118,306) obviously enhanced TG accumulation and repressed CAV1 in AML12 cells. Furthermore, the TG accumulation markedly increased by siRNA-mediated knockdown of CAV1 in AML12 cells. By bioinformatics prediction, AML12 cells were transfected of siRNA-118,306 obviously upregulated miR-295-5p. Transfection of miR-295-5p mimics significantly increased TG accumulation and obviously suppressed the target CAV1.ConclusionsThe results revealed that lncRNA Gm12664–001 attenuated hepatic lipid accumulation through negatively regulating miR-295-5p and enhancing CAV1 expression in AML12 cells.
Highlights
Non-alcoholic fatty liver (NAFLD) is a kind of clinical pathological syndrome characterized by excess deposition of fat in liver, which is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as free fatty acids (FFAs) storage and disposal [1]
High fat diet contributes to lipid accumulation in mice Compared with normal control, the mice in high fat diet group increased body weight and body fat rate in mice (Fig. 1a, b)
We found that the level of long non-coding RNAs (lncRNAs) Gm12664–001 was markedly increased after treatment with 300 μM stearic acid (SA) or 500 μM palmitic acid (PA) for 24 h in Alpha mouse liver 12 (AML12) cells (Fig. 2d)
Summary
Non-alcoholic fatty liver (NAFLD) is a kind of clinical pathological syndrome characterized by excess deposition of fat in liver, which is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as free fatty acids (FFAs) storage and disposal [1]. Correcting and decreasing the factors contributing to excessive accumulation of body fat, have been considered effective strategies to improve NAFLD. Acting as important regulatory molecules, lncRNAs show moderately evolutional conservation and specific transcription and have roles in transcriptional regulation, epigenetic gene regulation, and disease development, such as NAFLD [5]. Our study aims to investigate the mechanisms of lncRNA Gm12664–001 improved hepatic lipid accumulation-initiated NAFLD via regulating miR-295-5p and CAV1 in AML12 cells
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