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Diabetes. 2014 Sep;63(9):3141-8. doi: 10.2337/db13-1015. Epub 2014 Apr 10.

MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes.

Author information

1
Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
2
Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC.
3
KineMed, Inc., Emeryville, CA.
4
Department of Pediatrics, Boston Children's Hospital, Boston, MA.
5
Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN.
6
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC.
7
Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC praveen_sethupathy@med.unc.edu.

Abstract

MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological factors in complex disease, and promising drug targets. Recent reports suggest that miRNAs are critical regulators of pathways underlying the pathophysiology of type 2 diabetes. In this study, we demonstrate by deep sequencing and real-time quantitative PCR that hepatic levels of Foxa2 mRNA and miR-29 are elevated in a mouse model of diet-induced insulin resistance. We also show that Foxa2 and miR-29 are significantly upregulated in the livers of Zucker diabetic fatty (fa/fa) rats and that the levels of both returned to normal upon treatment with the insulin-sensitizing agent pioglitazone. We present evidence that miR-29 expression in human hepatoma cells is controlled in part by FOXA2, which is known to play a critical role in hepatic energy homeostasis. Moreover, we demonstrate that miR-29 fine-tunes FOXA2-mediated activation of key lipid metabolism genes, including PPARGC1A, HMGCS2, and ABHD5. These results suggest that miR-29 is an important regulatory factor in normal metabolism and may represent a novel therapeutic target in type 2 diabetes and related metabolic syndromes.

PMID:
24722248
PMCID:
PMC4141370
DOI:
10.2337/db13-1015
[Indexed for MEDLINE]
Free PMC Article
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