Long non-coding RNA G23Rik attenuates fasting-induced lipid accumulation in mouse liver.
Long non-coding RNA G23Rik attenuates fasting-induced lipid accumulation in mouse liver.
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长非编码RNA G23Rik可减轻禁食诱导的小鼠肝脏脂肪堆积。
DOI：
10.1016/j.mce.2022.111722
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发表时间：
2022-11-01
影响因子：
4.1
通讯作者：
Gonzalez, Frank J.
中科院分区：
文献类型：
--
作者：
Kim, Donghwan;Kim, Bora;Brocker, Chad N.;Karri, Kritika;Waxman, David J.;Gonzalez, Frank J.
过氧化物酶体增殖物激活受体α (PPARα)是肝脏脂质代谢和代谢应激的关键介质。最近的一项研究表明，ppar α依赖的长链非编码rna （lncRNAs）在禁食小鼠肝脏代谢应激和炎症的调节中发挥重要作用。本研究发现肝脏lncRNA 3930402G23Rik （G23Rik）在其启动子内具有活性过氧化物酶体增殖反应元件（PPREs），并直接受PPARα调控。虽然G23Rik RNA在多种组织中都有不同程度的表达，但该lncRNA的ppar α依赖性调控仅在肝脏中观察到。药理激活PPARα诱导G23Rik启动子处的PPARα募集，并显著增加肝脏G23Rik lncRNA表达。开发了G23Rik-null小鼠系，以进一步表征该lncRNA在肝脏中的功能。G23Rik-null小鼠在急性禁食后更容易发生肝脏脂质积累。组织学分析进一步显示脂滴明显积聚，中性甘油三酯和脂质的显著增加，肝切片油红O染色增强。g23rik缺失小鼠的肝脏胆固醇、非酯化脂肪酸和甘油三酯水平显著升高，并与脂质代谢相关基因Cd36的诱导有关。这些发现为lncRNA依赖机制提供了证据，PPARα通过lncRNA G23Rik诱导减少代谢应激下肝脏脂质积累。
Peroxisome proliferator-activated receptor α (PPARα) is a key mediator of lipid metabolism and metabolic stress in the liver. A recent study revealed that PPARα-dependent long non-coding RNAs (lncRNAs) play an important role in modulating metabolic stress and inflammation in the livers of fasted mice. Here hepatic lncRNA 3930402G23Rik (G23Rik) was found to have active peroxisome proliferator response elements (PPREs) within its promoter and is directly regulated by PPARα. Although G23Rik RNA was expressed to varying degrees in several tissues, the PPARα-dependent regulation of this lncRNA was only observed in the liver. Pharmacological activation of PPARα induced PPARα recruitment at the G23Rik promoter and a pronounced increase in hepatic G23Rik lncRNA expression. A G23Rik-null mouse line was developed to further characterize the function of this lncRNA in the liver. G23Rik-null mice were more susceptible to hepatic lipid accumulation in response to acute fasting. Histological analysis further revealed a pronounced buildup of lipid droplets and a significant increase in neutral triglycerides and lipids as indicated by enhance oil red O staining of liver sections. Hepatic cholesterol, non-esterified fatty acid, and triglyceride levels were significantly elevated in G23Rik-null mice and associated with induction of the lipid-metabolism related gene Cd36. These findings provide evidence for a lncRNA dependent mechanism by which PPARα attenuates hepatic lipid accumulation in response to metabolic stress through lncRNA G23Rik induction.
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影响因子：
2.9
作者：
Cortes-Lopez F;Sanchez-Mendoza A;Centurion D;Cervantes-Perez LG;Castrejon-Tellez V;Del Valle-Mondragon L;Soria-Castro E;Ramirez V;Sanchez-Lopez A;Pastelin-Hernandez G;Garcia-Niño WR;Sanchez-Aguilar M;Ibarra-Lara L
通讯作者：
Ibarra-Lara L
影响因子：
5.4
作者：
Grygiel-Górniak B
通讯作者：
Grygiel-Górniak B
影响因子：
29
作者：
Goodpaster BH;Sparks LM
通讯作者：
Sparks LM
影响因子：
4.8
作者：
Connerney, Jeannette;Lau-Corona, Dana;Waxman, David J.
通讯作者：
Waxman, David J.
影响因子：
4.4
作者：
Li, Jiali;Lu, Zhenyi;Su, Zhaoliang
通讯作者：
Su, Zhaoliang