miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.
miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.
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miR-212 下调通过靶向 FGF-21 有助于运动对非酒精性脂肪肝的保护作用
DOI：
10.1111/jcmm.12733
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发表时间：
2016-02
影响因子：
5.3
通讯作者：
Yang W
中科院分区：
文献类型：
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作者：
Xiao J;Bei Y;Liu J;Dimitrova-Shumkovska J;Kuang D;Zhou Q;Li J;Yang Y;Xiang Y;Wang F;Yang C;Yang W
非酒精性脂肪肝（NAFLD）与肥胖和生活方式有关，而运动对NAFLD有益。失调的microRNA（miRs）控制NAFLD的发病机制。然而，运动是否可以通过靶向microRNA预防NAFLD尚不清楚。在这项研究中，正常或高脂肪饮食（HF）小鼠要么进行16周的跑步计划，要么保持久坐不动。运动可减轻HF小鼠的肝脏脂肪变性。microRNA阵列和qRT-PCR显示，miR-212在HF肝脏中过表达，而运动降低。接下来，我们使用有/没有长链脂肪酸处理（±FFA）的HepG 2细胞研究了miR-212在脂肪生成中的作用。FFA增加HepG 2细胞中的miR-212。此外，miR-212促进HepG 2细胞中的脂肪生成（±FFA）。成纤维细胞生长因子（FGF）-21是脂质代谢的关键调节因子，在HepG 2细胞中，miR-212在蛋白水平上负调控FGF-21。同时，FFA在mRNA和蛋白水平下调HepG 2细胞中的FGF-21。此外，HF肝脏中的FGF-21蛋白水平降低，而体内运动则逆转。此外，siRNA-FGF-21消除了miR-212抑制剂在HepG 2细胞中的脂肪生成减少作用（±FFA），验证了FGF-21作为miR-212的靶基因。这些数据将运动和miR-212下调通过靶向FGF-21预防NAFLD的益处联系起来。
Non‐alcoholic fatty liver disease (NAFLD) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD. Dysregulated microRNAs (miRs) control the pathogenesis of NAFLD. However, whether exercise could prevent NAFLD via targeting microRNA is unknown. In this study, normal or high‐fat diet (HF) mice were either subjected to a 16‐week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. MicroRNA array and qRT‐PCR demonstrated that miR‐212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR‐212 in lipogenesis using HepG2 cells with/without long‐chain fatty acid treatment (±FFA). FFA increased miR‐212 in HepG2 cells. Moreover, miR‐212 promoted lipogenesis in HepG2 cells (±FFA). Fibroblast growth factor (FGF)‐21, a key regulator for lipid metabolism, was negatively regulated by miR‐212 at protein level in HepG2 cells. Meanwhile, FFA downregulated FGF‐21 both at mRNA and protein levels in HepG2 cells. Also, FGF‐21 protein level was reduced in HF liver, while reversed by exercise in vivo. Furthermore, siRNA‐FGF‐21 abolished the lipogenesis‐reducing effect of miR‐212 inhibitor in HepG2 cells (±FFA), validating FGF‐21 as a target gene of miR‐212. These data link the benefit of exercise and miR‐212 downregulation in preventing NAFLD via targeting FGF‐21.