miR-696 plays a role in hepatic gluconeogenesis in ob/ob mice by targeting PGC-1α.

Abstract

MicroRNAs (miRNAs or miRs) are known to play a vital role in type 2 diabetes, and peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is involved in the pathogenesis of hepatic insulin resistance. However, the correlation, if any, between PGC-1α and miRNAs in the disease has not yet been determined. Thus, in the present study, we aimed to examine the correlation between PGC-1α and miRNAs in diabetes. For this purpose, we used primary hepatocytes isolated from C57BL/6 mice and ob/ob mice. First, we found an inverse correlation between miR‑696 and PGC-1α protein levels in vivo. Second, in vitro evidence demonstrated that PGC-1α expression was significantly decreased by infection with pre-miR‑696-LV, whereas infection with anti-miR‑696-LV increased the PGC-1α protein levels. Third, a luciferase reporter assay confirmed that miR‑696 directly recognizes a specific location within the 3'-untranslated region of PGC-1α transcripts. Furthermore, the biological consequences of miR‑696 targeting PGC-1α were determined by measuring the expression levels of the characteristic hepatic gluconeogenic enzyme, PEPCK, which is regulated by PGC-1α in the liver via the coactivation of transcription factors. Taken together, our findings demonstrate that miR‑696 plays an important role in the development of hepatic gluconeogenesis and insulin resistance through the inhibition of PGC-1α translation in the liver.

• Authors: Zhijuan Fang, Peng Li, Wenhui Jia, Ting Jiang, Zhongyun Wang, Yang Xiang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 38 Issue 3 Pg. 845-52 (Sep 2016) ISSN: 1791-244X [Electronic] Greece
• PMID: 27432632 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MicroRNAs
• Mirn696 microRNA, mouse
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Phosphoenolpyruvate Carboxykinase (ATP)

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Base Sequence
• Blotting, Western
• Cells, Cultured
• Gene Expression Regulation
• Gluconeogenesis (genetics)
• HEK293 Cells
• Hepatocytes (cytology, metabolism)
• Humans
• Liver (cytology, metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Obese
• MicroRNAs (genetics)
• Models, Genetic
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (genetics, metabolism)
• Phosphoenolpyruvate Carboxykinase (ATP) (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction