MicroRNA-124 Regulates Fatty Acid and Triglyceride Homeostasis

Tyler A. Shaw; Ragunath Singaravelu; Megan H. Powdrill; Jordan Nhan; Nadine Ahmed; Dennis Özcelik; John Paul Pezacki

iScience (Dec 2018)

MicroRNA-124 Regulates Fatty Acid and Triglyceride Homeostasis

Tyler A. Shaw,
Ragunath Singaravelu,
Megan H. Powdrill,
Jordan Nhan,
Nadine Ahmed,
Dennis Özcelik,
John Paul Pezacki

Affiliations

Tyler A. Shaw: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Ragunath Singaravelu: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Megan H. Powdrill: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Jordan Nhan: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Nadine Ahmed: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Dennis Özcelik: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
John Paul Pezacki: Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada; Corresponding author

Journal volume & issue: Vol. 10
pp. 149 – 157

Abstract

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Summary: MicroRNAs (miRNAs) are part of a complex regulatory network that modulates cellular lipid metabolism. Here, we identify miR-124 as a regulator of triglyceride (TG) metabolism. This study advances our knowledge of the role of miR-124 in human hepatoma cells. Transcriptional profiling of Huh7.5 cells overexpressing miR-124 reveals enrichment for host factors involved in fatty acid oxidation among repressed miRNA targets. In addition, miR-124 down-regulates arylacetamide deacetylase (AADAC) and adipose triglyceride lipase, lipases proposed to mediate breakdown of hepatic TG stores for lipoprotein assembly and mitochondrial β-oxidation. Consistent with the inhibition of TG and fatty acid catabolism, miR-124 expression promotes cellular TG accumulation. Interestingly, miR-124 inhibits the production of hepatitis C virus, a virus that hijacks lipid pathways during its life cycle. Antiviral activity of miR-124 is consistent with repression of AADAC, a pro-viral host factor. Overall, our data highlight miR-124 as a novel regulator of TG metabolism in human hepatoma cells. : Biological Sciences; Biochemistry; Biochemical Mechanism Subject Areas: Biological Sciences, Biochemistry, Biochemical Mechanism

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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