Inhibition of dexamethasone-induced fatty liver development by reducing miR-17-5p levels

William W. Du, Fengqiong Liu, Sze Wan Shan, Xindi Cindy Ma, Shaan Gupta, Tianru Jin, David Spaner, Sergey N. Krylov, Yaou Zhang, Wenhua Ling, Burton B. Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

25 Citations (Scopus)


Steatosis is a pivotal event in the initiation and progression of nonalcoholic fatty liver disease (NAFLD) which can be driven by peroxisome proliferator-activated receptor-α (PPAR-α) dysregulation. Through examining the effect of PPAR-α on fatty liver development, we found that PPAR-α is a target of miR-17-5p. Transgenic mice expressing miR-17 developed fatty liver and produced higher levels of triglyceride and cholesterol but lower levels of PPAR-α. Ectopic expression of miR-17 enhanced cellular steatosis. Gain-of-function and loss-of-function experiments confirmed PPAR-α as a target of miR-17-5p. On the other hand, PPAR-α bound to the promoter of miR-17 and promoted its expression. The feed-back loop between miR-17-5p and PPAR-α played a key role in the induction of steatosis and fatty liver development. Mice with high levels of miR-17-5p were sensitive to Dexamethasone-induced fatty liver formation. Inhibition of miR-17-5p suppressed this process and enhanced PPAR-α expression in mice treated with Dexamethasone. Clofibrate, Ciprofibrate, and WY-14643: three agents used for treatment of metabolic disorders, were found to promote PPAR-α expression while decreasing miR-17-5p levels and inhibiting steatosis. Our studies show that miR-17-5p inhibitor and agents used in metabolic disorders may be applied in combination with Dexamethasone in the treatment of anti-inflammation, immunosuppression, and cancer patients.

Original languageEnglish
Pages (from-to)1222-1233
Number of pages12
JournalMolecular Therapy
Issue number7
Publication statusPublished - 1 Jul 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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