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Article (Scientific journals)
miR-322 regulates insulin signaling pathway and protects against metabolic syndrome-induced cardiac dysfunction in mice.
Marchand, Alexandre; Atassi, Fabrice; Mougenot, Nathalie et al.
2016In Biochimica et biophysica acta, 1862 (4), p. 611-621
Peer reviewed


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Keywords :
Animals; Dependovirus; Dietary Fats/adverse effects/pharmacology; Genetic Vectors; Heart Diseases/genetics/metabolism/pathology/therapy; Humans; Hyperinsulinism/genetics/metabolism/pathology/therapy; Hyperlipidemias/genetics/metabolism/pathology/therapy; Insulin/genetics/metabolism; Male; Metabolic Syndrome/genetics/metabolism/pathology/therapy; Mice; Mice, Obese; MicroRNAs/biosynthesis/genetics; Rats; Rats, Wistar; Signal Transduction; Transduction, Genetic; Cardiomyopathy; High fat diet; Insulin pathway; Metabolic syndrome; MicroRNA
Abstract :
[en] We identified murine miR-322, orthologous to human miR-424, as a new regulator of insulin receptor, IGF-1 receptor and sirtuin 4 mRNA in vitro and in vivo in the heart and found that miR-322/424 is highly expressed in the heart of mice. C57Bl/6N mice fed 10weeks of high fat diet (HFD) presented signs of cardiomyopathy and a stable miR-322 cardiac level while cardiac function was slightly affected in 11week-old ob/ob which overexpressed miR-322. We thus hypothesized that mmu-miR-322 could be protective against cardiac consequences of hyperinsulinemia and hyperlipidemia. We overexpressed or knocked-down mmu-miR-322 using AAV9 and monitored cardiac function in wild-type C57Bl/6N mice fed a control diet (CD) or a HFD and in ob/ob mice. The fractional shortening progressively declined while the left ventricle systolic diameter increased in HFD mice infected with an AAVcontrol or with an AAVsponge (decreasing miR-322 bioavailability) but also in ob/ob mice infected with AAVsponge. Similar observations were also found in CD-fed mice infected with AAVsponge. On the contrary over-expressing miR-322 with AAVmiR-322 was efficient in protecting the heart from HFD effects in C57Bl/6N mice. This cardioprotection could be associated with the regulation of identified targets IGF1R, INSR and CD1, a decrease in insulin signaling pathway and an enrichment of genes involved in mitochondrial function and fatty acid oxidation as demonstrated by transcriptome analysis. Altogether, these results emphasize miR-322 as a new potential therapeutic target against cardiac consequences of metabolic syndrome, which represents an increasing burden in the western countries.
Disciplines :
Genetics & genetic processes
Author, co-author :
Marchand, Alexandre
Atassi, Fabrice
Mougenot, Nathalie
Clergue, Michel
Codoni, Veronica ;  Institut National de la Santé et de la Recherche Médicale - INSERM > Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche en Santé 1166, F-75013 Paris
Berthuin, Jeremy
Proust, Carole
Trégouët, David-Alexandre
Hulot, Jean-Sébastien
Lompré, Anne-Marie
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Title :
miR-322 regulates insulin signaling pathway and protects against metabolic syndrome-induced cardiac dysfunction in mice.
Publication date :
Journal title :
Biochimica et biophysica acta
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Peer reviewed :
Peer reviewed
Commentary :
Copyright © 2016. Published by Elsevier B.V.


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