Methylation of lncSHGL promotes adipocyte differentiation by regulating miR-149/Mospd3 axis.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2023-11-01 Epub Date: 2024-01-18 DOI:10.1080/15384101.2023.2287367
Xianwei Huang, Xiong Liu, Jiyan Lin
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引用次数: 0

Abstract

Obesity poses significant health risks and can negatively impact an individual's quality of life. The human obesity phenotype results from the differentiation of pre-adipocytes into adipocytes, which leads to hypertrophy and hyperplasia in adipose tissue. The molecular mechanisms by which long non-coding RNAs (lncRNAs) modulate adipocyte differentiation, a process implicated in obesity development, remain poorly characterized. A lncRNA which suppressed the hepatic gluconeogenesis and lipogenesis (lncSHGL) was newly identified. Our research aims to elucidate the functional role and mechanistic underpinnings of suppressor of lncSHGL in adipocyte differentiation. We observed that lncSHGL expression progressively diminished during 3T3-L1 differentiation and was downregulated in the liver and perirenal adipose tissue of ob/ob mice. lncSHGL acts as a molecular sponge for miR-149, with Mospd3 identified as a target of miR-149.Overexpression of lncSHGL and inhibition of miR-149 led to suppressed 3T3-L1 proliferation, decreased lipid droplet accumulation, and attenuated promoter activity of PPARγ2 and C/EBPα. These changes consequently resulted in reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα, as well as inhibited the PI3K/AKT/mTOR signaling pathway. In contrast, lncSHGL suppression yielded opposing outcomes. Moreover, the effects of lncSHGL overexpression and miR-149 inhibition on reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα were reversible upon miR-149 overexpression and Mospd3 suppression. These findings were further validated in vivo. We also discovered a significant increase in methylation levels during 3T3-L1 differentiation, with lncSHGL highly expressed in the presence of a methylation inhibitor. In conclusion. lncSHGL methylation facilitates adipocyte differentiation by modulating the miR-149/Mospd3 axis. Targeting lncSHGL expression may represent a promising therapeutic strategy for obesity-associated adipogenesis, particularly in the context of fatty liver disease.

lnccshgl的甲基化通过调节miR-149/Mospd3轴促进脂肪细胞分化。
肥胖会带来严重的健康风险,并对个人的生活质量产生负面影响。人类肥胖表型是由于前脂肪细胞向脂肪细胞分化,导致脂肪组织肥大和增生。长链非编码rna (lncRNAs)调节脂肪细胞分化的分子机制(这一过程与肥胖的发生有关)仍然缺乏明确的特征。新发现了一个抑制肝脏糖异生和脂肪生成的lncRNA (lncSHGL)。本研究旨在阐明lncSHGL抑制因子在脂肪细胞分化中的功能作用及其机制基础。我们观察到lncSHGL的表达在3T3-L1分化过程中逐渐减少,并在ob/ob小鼠的肝脏和肾周脂肪组织中下调。lncSHGL作为miR-149的分子海绵,其中Mospd3被确定为miR-149的靶标。lnccshgl的过表达和miR-149的抑制导致3T3-L1增殖受到抑制,脂滴积累减少,PPARγ2和C/EBPα启动子活性减弱。这些变化导致Cyclin D1、LPL、PPARγ2、AP2和C/EBPα的表达降低,并抑制PI3K/AKT/mTOR信号通路。相比之下,lncSHGL抑制产生相反的结果。此外,lnccshgl过表达和miR-149抑制对Cyclin D1、LPL、PPARγ2、AP2和C/EBPα表达降低的影响在miR-149过表达和Mospd3抑制后是可逆的。这些发现在体内得到了进一步的验证。我们还发现,在3T3-L1分化过程中,甲基化水平显著增加,lncSHGL在甲基化抑制剂存在下高度表达。在结论。nlshgl甲基化通过调节miR-149/Mospd3轴促进脂肪细胞分化。靶向lnncshgl表达可能是一种有希望的治疗肥胖相关脂肪生成的策略,特别是在脂肪肝疾病的背景下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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