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Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)

This study examined the similarities in microRNA profiles between fasted and fluoxetine (FLX) exposed zebrafish and downstream target transcripts and biological pathways. Using a custom designed microarray targeting 270 zebrafish miRNAs, we identified 9 differentially expressed miRNAs targeting tran...

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Autores principales: Craig, Paul M., Trudeau, Vance L., Moon, Thomas W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994061/
https://www.ncbi.nlm.nih.gov/pubmed/24751937
http://dx.doi.org/10.1371/journal.pone.0095351
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author Craig, Paul M.
Trudeau, Vance L.
Moon, Thomas W.
author_facet Craig, Paul M.
Trudeau, Vance L.
Moon, Thomas W.
author_sort Craig, Paul M.
collection PubMed
description This study examined the similarities in microRNA profiles between fasted and fluoxetine (FLX) exposed zebrafish and downstream target transcripts and biological pathways. Using a custom designed microarray targeting 270 zebrafish miRNAs, we identified 9 differentially expressed miRNAs targeting transcripts in biological pathways associated with anabolic metabolism, such as adipogenesis, cholesterol biosynthesis, triacylglycerol synthesis, and insulin signaling. Exposure of female zebrafish to 540 ng/L FLX, an environmentally relevant concentration and a known metabolic repressor, increased specific miRNAs indicating greater inhibition of these pathways in spite of continued feeding. Further examination revealed two specific miRNAs, dre-let-7d and dre-miR-140-5p, were predicted in silico to bind to a primary regulator of metabolism, adenosine monophosphate-activated protein kinase (AMPK), and more specifically the two isoforms of the catalytic subunit, AMPKα1 and α2, respectively. Real-time analysis of the relative transcript abundance of the α1 and α2 mRNAs indicated a significant inverse relationship between specific miRNA and target transcript. This suggests that AMPK-related pathways may be compromised during FLX exposure as a result of increased miRNA abundance. The mechanism by which FLX regulates miRNA abundance is unknown but may be direct at the liver. The serotonin transporter, slc6a4, is the target of FLX and other selective serotonin reuptake inhibitors (SSRI) and it was found to be expressed in the liver, although treatment did not alter expression of this transporter. Exposure to FLX disrupts key hepatic metabolic pathways, which may be indicative of reduced overall fitness and these effects may be linked to specific miRNA abundance. This has important implications for the heath of fish because concentrations of SSRIs in aquatic ecosystems are continually increasing.
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spelling pubmed-39940612014-04-25 Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK) Craig, Paul M. Trudeau, Vance L. Moon, Thomas W. PLoS One Research Article This study examined the similarities in microRNA profiles between fasted and fluoxetine (FLX) exposed zebrafish and downstream target transcripts and biological pathways. Using a custom designed microarray targeting 270 zebrafish miRNAs, we identified 9 differentially expressed miRNAs targeting transcripts in biological pathways associated with anabolic metabolism, such as adipogenesis, cholesterol biosynthesis, triacylglycerol synthesis, and insulin signaling. Exposure of female zebrafish to 540 ng/L FLX, an environmentally relevant concentration and a known metabolic repressor, increased specific miRNAs indicating greater inhibition of these pathways in spite of continued feeding. Further examination revealed two specific miRNAs, dre-let-7d and dre-miR-140-5p, were predicted in silico to bind to a primary regulator of metabolism, adenosine monophosphate-activated protein kinase (AMPK), and more specifically the two isoforms of the catalytic subunit, AMPKα1 and α2, respectively. Real-time analysis of the relative transcript abundance of the α1 and α2 mRNAs indicated a significant inverse relationship between specific miRNA and target transcript. This suggests that AMPK-related pathways may be compromised during FLX exposure as a result of increased miRNA abundance. The mechanism by which FLX regulates miRNA abundance is unknown but may be direct at the liver. The serotonin transporter, slc6a4, is the target of FLX and other selective serotonin reuptake inhibitors (SSRI) and it was found to be expressed in the liver, although treatment did not alter expression of this transporter. Exposure to FLX disrupts key hepatic metabolic pathways, which may be indicative of reduced overall fitness and these effects may be linked to specific miRNA abundance. This has important implications for the heath of fish because concentrations of SSRIs in aquatic ecosystems are continually increasing. Public Library of Science 2014-04-21 /pmc/articles/PMC3994061/ /pubmed/24751937 http://dx.doi.org/10.1371/journal.pone.0095351 Text en © 2014 Craig et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Craig, Paul M.
Trudeau, Vance L.
Moon, Thomas W.
Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title_full Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title_fullStr Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title_full_unstemmed Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title_short Profiling Hepatic microRNAs in Zebrafish: Fluoxetine Exposure Mimics a Fasting Response That Targets AMP-Activated Protein Kinase (AMPK)
title_sort profiling hepatic micrornas in zebrafish: fluoxetine exposure mimics a fasting response that targets amp-activated protein kinase (ampk)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994061/
https://www.ncbi.nlm.nih.gov/pubmed/24751937
http://dx.doi.org/10.1371/journal.pone.0095351
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