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Changes in circulating miRNA19a-3p precede insulin resistance programmed by intra-uterine growth retardation in mice

dc.rights.licenseopenen_US
dc.contributor.authorSAGET, S.
dc.contributor.authorCONG, R.
dc.contributor.authorDECOURTYE, L.
dc.contributor.authorENDALE, M. L.
dc.contributor.authorMARTINERIE, L.
dc.contributor.authorGIRARDET, C.
dc.contributor.authorPERRET, C.
dc.contributor.authorCLEMESSY, M.
dc.contributor.authorLENEUVE, P.
dc.contributor.authorDINARD, L.
dc.contributor.authorMOHAND OUMOUSSA, B.
dc.contributor.authorFARABOS, D.
dc.contributor.authorLAMAZIERE, A.
dc.contributor.authorLOMBES, M.
dc.contributor.authorMOLDES, M.
dc.contributor.authorFEVE, B.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorLE BOUC, Y.
dc.contributor.authorKAPPELER, L.
dc.date.accessioned2021-03-16T14:46:14Z
dc.date.available2021-03-16T14:46:14Z
dc.date.issued2020-12
dc.identifier.issn2212-8778 (Electronic) 2212-8778 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26695
dc.description.abstractEnINTRODUCTION: Individuals born with intrauterine growth retardation (IUGR) are more prone to cardio-metabolic diseases as adults. The prevalence of IUGR (5 to 7% of births in developed countries) may herald a worsening of the current worldwide epidemic of obesity and related comorbidities. METHODS: We used a preclinical mouse model of induced IUGR, in which we modulated the nutrition of the pups during the suckling period, to modify their susceptibility to cardio-metabolic diseases in adulthood. Mice born with IUGR that were overfed (IUGR-O) during lactation rapidly developed obesity, hepatic steatosis and insulin resistance, by three months of age, whereas those subjected to nutrition restriction during lactation (IUGR-R) remained permanently thin and highly sensitive to insulin. Mice born with IUGR and fed normally during lactation (IUGR-N) presented an intermediate phenotype and developed insulin resistance by 12 months of age. Molecular alterations to the insulin signaling pathway with an early onset were observed in the livers of adult IUGR-N mice, nine months before the appearance of insulin resistance. The implication of epigenetic changes was revealed by ChIP sequencing, with both posttranslational H3K4me3 histone modifications and microRNAs involved. CONCLUSION: These two changes lead to the coherent regulation of insulin signaling, with a decrease in Akt gene transcription associated with an increase in the translation of its inhibitor, Pten. Moreover, we found that the levels of the implicated miRNA19a-3p also decreased in the blood of young adult IUGR mice nine months before the appearance of insulin resistance, suggesting a possible role for this miRNA as an early circulating biomarker of metabolic fate of potential use for precision medicine.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enChanges in circulating miRNA19a-3p precede insulin resistance programmed by intra-uterine growth retardation in mice
dc.title.alternativeMol Metaben_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.molmet.2020.101083en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32956848en_US
bordeaux.journalMolecular metabolismen_US
bordeaux.page101083en_US
bordeaux.volume42en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03170970
hal.version1
hal.date.transferred2021-03-16T14:46:20Z
hal.exporttrue
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