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Myeloid ecotropic viral integration site 1 (MEIS1) is a transcription factor that promotes glycolysis in hematopoietic stem cells. We reasoned that MEIS1 could have a similar role in the developing heart. We hypothesized that suppression of MEIS1 expression in fetal sheep cardiomyocytes leads to a metabolic switch as found at birth. Expression of MEIS1 was assayed in left ventricular cardiac tissue and primary cultures of cardiomyocytes from fetal (100\u2010 and 135\u2010d gestation, term = 145 d), neonatal, and adult sheep. Cultured cells were treated with short interfering RNA (siRNA) to suppress MEIS1. Oxygen consumption rate was assessed with the Seahorse metabolic flux analyzer, and mitochondrial activity was assessed by staining cells with MitoTracker Orange. Cardiomyocyte respiratory capacity increased with advancing age concurrently with decreased expression of MEIS1. MEIS1 suppression with siRNA increased maximal oxygen consumption in fetal cells but not in postnatal cells. Mitochondrial activity was increased and expression of glycolytic genes decreased when MEIS1 expression was suppressed. Thus, we conclude that MEIS1 is a key regulator of cardiomyocyte metabolism and that the normal down\u2010regulation of MEIS1 with age underlies a gradual switch to oxidative metabolism.\u2014Lindgren, I. M., Drake, R. R., Chattergoon, N. N., Thornburg, K. L. Down\u2010regulation of MEIS1 promotes the maturation of oxidative phosphorylation in perinatal cardiomyocytes. FASEB J. 33, 7417\u20137426 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801330rr","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T19:05:21Z","timestamp":1552935921000},"page":"7417-7426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Down\u2010regulation of MEIS1 promotes the maturation of oxidative phosphorylation in perinatal cardiomyocytes"],"prefix":"10.1096","volume":"33","author":[{"given":"Isa M.","family":"Lindgren","sequence":"first","affiliation":[{"name":"Center for Developmental Health Knight Cardiovascular Institute Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel R.","family":"Drake","sequence":"additional","affiliation":[{"name":"Center for Developmental Health Knight Cardiovascular Institute Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha N.","family":"Chattergoon","sequence":"additional","affiliation":[{"name":"Center for Developmental Health Knight Cardiovascular Institute Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent L.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Center for Developmental Health Knight Cardiovascular Institute Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013516"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.41.2.343"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.42.6.839"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1203\/00006450-198712000-00001","article-title":"Fetal lamb ventricles respond differently to filling and arterial pressures and to in utero ventilation","volume":"22","author":"Relier M. 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