{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:15:23Z","timestamp":1783548923047,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK084842"],"award-info":[{"award-number":["R01 DK084842"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["2023-67015-40838"],"award-info":[{"award-number":["2023-67015-40838"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"USDA\/National Institute of Food and Agriculture","award":["R01 DK084842"],"award-info":[{"award-number":["R01 DK084842"]}]},{"name":"USDA\/National Institute of Food and Agriculture","award":["2023-67015-40838"],"award-info":[{"award-number":["2023-67015-40838"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fetuses with intrauterine growth restriction (FGR) have impaired oxidative and energy metabolism, with persistent consequences on their postnatal development. In this study, we test the hypothesis that FGR skeletal muscle has lower mitochondrial respiration rate and alters the transcriptomic profiles associated with energy metabolism in an ovine model. At late gestation, mitochondrial oxygen consumption rates (OCRs) and transcriptome profiles were evaluated in the skeletal muscle collected from FGR and control fetuses. The ex vivo mitochondrial OCRs were reduced (p &lt; 0.01) in permeabilized FGR soleus muscle compared to the control muscle but only with pyruvate as the metabolic substrate. Mitochondrial OCRs were similar between the FGR and control groups for palmitoyl-carnitine (fatty acid-driven) or pyruvate plus palmitoyl-carnitine metabolic substrates. A total of 2284 genes were differentially expressed in the semitendinosus muscle from growth restricted fetuses (false discovery rate (FDR) \u2264 0.05). A pathway analysis showed that the upregulated genes (FGR compared to control) were overrepresented for autophagy, HIF-1, AMPK, and FOXO signaling pathways (all with an FDR &lt; 0.05). In addition, the expression of genes modulating pyruvate\u2019s entry into the TCA cycle was downregulated, whereas the genes encoding key fatty acid oxidation enzymes were upregulated in the FGR muscle. These findings show that FGR skeletal muscle had attenuated mitochondrial pyruvate oxidation, possibly associated with the inability of pyruvate to enter into the TCA cycle, and that fatty acid oxidation might compensate for the attenuated energy metabolism. The current study provided phenotypic and molecular evidence for adaptive deficiencies in FGR skeletal muscle.<\/jats:p>","DOI":"10.3390\/ijms242115760","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T12:50:42Z","timestamp":1698670242000},"page":"15760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Decreased Pyruvate but Not Fatty Acid Driven Mitochondrial Respiration in Skeletal Muscle of Growth Restricted Fetal Sheep"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3055-6275","authenticated-orcid":false,"given":"Weicheng","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Kelly","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa I.","family":"Luna-Ramirez","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Bidwell","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-0439","authenticated-orcid":false,"given":"Sean W.","family":"Limesand","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1136\/bmj.306.6875.422","article-title":"The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life","volume":"306","author":"Barker","year":"1993","journal-title":"Br. 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