Zhang Ying, Zhao Ya-Ping, Gao Yuan-Fu, Fan Zhong-Min, Liu Meng-Yuan, Cai Xiao-Yi, Xia Zheng-Kun, Gao Chun-Lin
Department of Pediatrics, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
Department of Pediatrics, The 82nd Hospital of the People's Liberation Army, Huai'an, Jiangsu 223001, P.R. China.
Mol Med Rep. 2015 May;11(5):3834-41. doi: 10.3892/mmr.2014.3124. Epub 2014 Dec 22.
MicroRNA‑106b (miR‑106b) is reported to correlate closely with skeletal muscle insulin resistance. In the current study the effect of miR‑106b on palmitic acid (PA)‑induced mitochondrial dysfunction and insulin resistance was investigated in C2C12 myotubes via the silencing of miR‑106b. MiR‑106b expression was increased under PA treatment, while miR‑106b loss of function improved insulin sensitivity by upregulating its target mitofusin‑2 (Mfn2) in C2C12 myocytes. Furthermore, miR‑106b loss of function partly improved mitochondrial morphological lesions and increased the levels of mitochondial DNA and intracellular adenosine triphosphate that had been impaired by PA exposure in C2C12 myocytes. MiR‑106b loss of function attenuated the levels of intracellular reactive oxygen species (ROS), and upregulated the expression levels of the estrogen‑related receptor (ERR)‑α/peroxisome proliferative activated receptor γ coactivator (PGC)‑1α/Mfn2 axis under PA exposure. In addition, miR‑106b negatively regulated skeletal muscle mitochondrial function and insulin sensitivity under PA‑induced insulin resistance by targeting Mfn2, which may be associated with reduced ROS and upregulation of the ERR‑α/PGC‑1α/Mfn2 axis.
据报道，微小RNA-106b（miR-106b）与骨骼肌胰岛素抵抗密切相关。在本研究中，通过沉默miR-106b，在C2C12肌管中研究了miR-106b对棕榈酸（PA）诱导的线粒体功能障碍和胰岛素抵抗的影响。在PA处理下，miR-106b表达增加，而miR-106b功能缺失通过上调其靶标线粒体融合蛋白2（Mfn2）改善了C2C12心肌细胞的胰岛素敏感性。此外，miR-106b功能缺失部分改善了线粒体形态损伤，并增加了C2C12心肌细胞中因PA暴露而受损的线粒体DNA水平和细胞内三磷酸腺苷水平。miR-106b功能缺失减弱了细胞内活性氧（ROS）水平，并在PA暴露下上调了雌激素相关受体（ERR）-α/过氧化物酶体增殖物激活受体γ共激活因子（PGC）-1α/Mfn2轴的表达水平。此外，miR-106b通过靶向Mfn2在PA诱导的胰岛素抵抗下负向调节骨骼肌线粒体功能和胰岛素敏感性，这可能与ROS减少和ERR-α/PGC-1α/Mfn2轴上调有关。
