Department of Infectious Diseases, Shanghai Fifth People's Hospital, Fudan University, No. 128 Ruili Road, Shanghai, 200240, China.
Appl Biochem Biotechnol. 2021 May;193(5):1469-1481. doi: 10.1007/s12010-021-03486-z. Epub 2021 Jan 23.
Inhibition of lipid accumulation is the key step to prevent nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis. We aimed to study the effect of low-molecular-weight citrus pectin (LCP) against lipid accumulation and the underlying mechanism. Oleic acid (OA)-induced lipid deposition in HepG2 cells was applied to mimic in vitro model of lipid accumulation. Oil Red O (ORO) stain result showed lipid accumulation was significantly reduced, and levels of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase-1 (CPT-1), involved in triacylglycerol catabolism and fatty acid β-oxidation, detected by RT-qPCR were increased after OA-stimulated HepG2 cells treated with LCP. RNA sequencing analysis identified 740 differentially expressed genes (DEGs) in OA-stimulated HepG2 cells treated with the LCP group (OA+LCP group), and bioinformatics analysis indicated that some DEGs were enriched in lipid metabolism-related processes and pathways. The expression of the top 8 known DEGs in the OA+LCP group was then verified by RT-qPCR, which showed that fold change (abs) of METTL7B was the highest among the 8 candidates. In addition, overexpression of METTL7B in HepG2 cells significantly inhibited the lipid accumulation and enhanced levels of ATGL and CPT-1. In conclusion, LCP inhibited lipid accumulation through the upregulation of METTL7B, and further enhancement of ATGL and CPT-1 levels. LCP is expected to develop as a promising agent to ameliorate fat accumulation in NAFL.
抑制脂质积累是防止非酒精性脂肪肝（NAFL）进展为非酒精性脂肪性肝炎的关键步骤。我们旨在研究低分子量柑橘果胶（LCP）对脂质积累的影响及其潜在机制。应用油酸（OA）诱导的 HepG2 细胞脂质沉积来模拟体外脂质积累模型。油红 O（ORO）染色结果表明，LCP 处理 OA 刺激的 HepG2 细胞后，脂质积累明显减少，参与甘油三酯分解代谢和脂肪酸β氧化的脂肪甘油三酯脂肪酶（ATGL）和肉碱棕榈酰转移酶-1（CPT-1）的水平通过 RT-qPCR 检测到增加。RNA 测序分析鉴定出 OA 刺激的 HepG2 细胞中经 LCP 处理的 740 个差异表达基因（DEGs）（OA+LCP 组），生物信息学分析表明，一些 DEGs 富集在脂质代谢相关过程和途径中。然后通过 RT-qPCR 验证 OA+LCP 组中前 8 个已知 DEGs 的表达，结果显示 METTL7B 的倍数变化（abs）在 8 个候选基因中最高。此外，在 HepG2 细胞中过表达 METTL7B 可显著抑制脂质积累并提高 ATGL 和 CPT-1 的水平。总之，LCP 通过上调 METTL7B 抑制脂质积累，进一步增强 ATGL 和 CPT-1 的水平。LCP 有望开发成为改善 NAFL 中脂肪堆积的有前途的药物。
