Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 34, Issue 6, Pages 1983-1997Publisher
KARGER
DOI: 10.1159/000366394
Keywords
NAFLD; miRNA; Human hepatocyte; HepG2 cells; Deep sequencing
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Funding
- National Natural Science Foundation of China [81270938]
- Zhejiang Provincial Key Medical Disciplines (Innovation Discipline) [11-CX24]
- Zhejiang Province key scientific and technological innovation team [2010R50050]
- National Key Technology R&D Program of China [2012BAI02B03]
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Background/Aim: Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). Methods: Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Results: Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change > 1.5) and 12 down-regulated miRNAs (fold change < 0.5). Among the abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors. Conclusion: These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD. Copyright (C) 2014 S. Karger AG, Basel.
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