miR204 potentially promotes non-alcoholic fatty liver disease by inhibition of cpt1a in mouse hepatocytes.
miR204 potentially promotes non-alcoholic fatty liver disease by inhibition of cpt1a in mouse hepatocytes.
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DOI：
10.1038/s42003-022-03945-1
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发表时间：
2022-09-21
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
非酒精性脂肪性肝病（NAFLD）与肝脏代谢功能障碍有关。然而，miR 204在NAFLD发展中的机制作用尚不清楚。我们研究了miR 204在NAFLD演变中的功能意义。与饲喂ND或HFD的WT小鼠相比，饲喂正常饮食（ND）或HFD的IDH 2 KO小鼠的体重、附睾脂肪垫重量、肝脏中的脂滴、血液参数和炎症增加。此外，miR 204的表达在IDH 2缺陷的小鼠中增加。通过IDH 2缺陷增加的miR 204调节肉毒碱棕榈酰转移酶1a（cpt 1a）的合成，其抑制脂肪酸β-氧化。miR 204的抑制通过激活CPT 1a表达来防止两个脂肪酸相关基因的分解，这减少了肝脏中的脂滴、炎性细胞因子、附睾脂肪垫重量、血液参数。IDH 2缺乏导致的miR 204增加通过调节肝脏脂肪酸代谢和炎症促进HFD诱导的NAFLD的发病机制。miR 204被发现抑制小鼠肝细胞中的cpt 1a，这可能在促进非酒精性脂肪肝疾病中发挥作用。
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic metabolism dysfunction. However, the mechanistic role of miR204 in the development of NAFLD is unknown. We investigate the functional significance of miR204 in the evolution of NAFLD. IDH2 KO mice feed a normal diet (ND) or HFD increased body weight, epididymal fat-pad weight, lipid droplet in liver, blood parameter and inflammation compared to WT mice fed a ND or HFD. Moreover, the expression of miR204 is increased in mice with IDH2 deficiency. Increased miR204 by IDH2 deficiency regulates carnitine palmitoyltransferase 1a (cpt1a) synthesis, which inhibits fatty acid β-oxidation. Inhibition of miR204 prevents the disassembly of two fatty acid-related genes by activating CPT1a expression, which decreases lipid droplet in liver, inflammatory cytokines, epididymal fat pad weight, blood parameters. Increased miR204 by IDH2 deficiency promotes the pathogenesis of HFD-induced NAFLD by regulating hepatic fatty acid metabolism and inflammation. miR204 is found to inhibit cpt1a in mouse hepatocytes, which could play a role in promoting non-alcoholic fatty liver disease.
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影响因子：
7.7
作者：
Galic S;Loh K;Murray-Segal L;Steinberg GR;Andrews ZB;Kemp BE
通讯作者：
Kemp BE
影响因子：
4.5
作者：
McInnes J
通讯作者：
McInnes J
影响因子：
2.9
作者：
Liang Y;Tian WY;Huang JJ;Gao LX;Fan XH
通讯作者：
Fan XH
影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
33.5
作者：
Lu X;Wei Y;Liu F
通讯作者：
Liu F