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

doi:10.1016/j.isci.2018.11.028

MicroRNA-124 Regulates Fatty Acid and Triglyceride Homeostasis

iScience. 2018 Dec 21:10:149-157. doi: 10.1016/j.isci.2018.11.028. Epub 2018 Nov 20.

Authors

Tyler A Shaw¹, Ragunath Singaravelu¹, Megan H Powdrill¹, Jordan Nhan¹, Nadine Ahmed¹, Dennis Özcelik¹, John Paul Pezacki²

Affiliations

¹ Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.
² Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada. Electronic address: john.pezacki@uottawa.ca.

Abstract

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.

Keywords: Biochemical Mechanism; Biochemistry; Biological Sciences.