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Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p &lt; 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p &lt; 0.05) circulating TNF\u03b1 observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p &lt; 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24\u201339% lighter (p &lt; 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p &lt; 0.05) IL6R and reduced (p &lt; 0.05) \u03b22 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished \u03b22 adrenergic sensitivity. Although IL6R remained elevated, \u03b22 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention.<\/jats:p>","DOI":"10.3390\/metabo14060340","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T07:33:20Z","timestamp":1718696000000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADR\u03b22 Content, and Improved Myoblast Function and Muscle Growth"],"prefix":"10.3390","volume":"14","author":[{"given":"Haley N.","family":"Beer","sequence":"first","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor A.","family":"Lacey","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah S.","family":"Most","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zena M.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo C.","family":"Grijalva","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen S.","family":"Marks-Nelson","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty B.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Meat Science and Muscle Biology, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-8555","authenticated-orcid":false,"given":"Jessica L.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genetics, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin T.","family":"Yates","sequence":"additional","affiliation":[{"name":"Stress Physiology Laboratory, Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-13-0567","article-title":"Endocrine regulation of fetal skeletal muscle growth: Impact on future metabolic health","volume":"221","author":"Brown","year":"2014","journal-title":"J. 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