Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRβ2 Content, and Improved Myoblast Function and Muscle Growth

Authors

Haley Beer, University of Nebraska-LincolnFollow
Taylor A. Lacey, University of Nebraska Lincoln
Rachel L. Gibbs, University of Nebraska Lincoln
Micah S. Most, University of Nebraska Lincoln
Zena M. Hicks, University of Nebraska Lincoln
Pablo C. Grijalva, University of Nebraska Lincoln
Eileen S. Marks-Nelson, University of Nebraska-LincolnFollow
Ty B. Schmidt, University of Nebraska-LincolnFollow
Jessica Lynn Petersen, University of Nebraska - LincolnFollow
Dustin T. Yates, University of Nebraska LincolnFollow

Document Type

Article

Date of this Version

6-18-2024

Citation

Beer, H.N.; Lacey, T.A.; Gibbs, R.L.; Most, M.S.; Hicks, Z.M.; Grijalva, P.C.; Marks-Nelson, E.S.; Schmidt, T.B.; Petersen, J.L.; Yates, D.T. Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRβ2 Content, and Improved Myoblast Function and Muscle Growth. Metabolites 2024, 14, 340. https://doi.org/10.3390/ metabo14060340

Comments

Open access.

Abstract

Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. 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 < 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 < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 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 24–39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) β2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished β2 adrenergic sensitivity. Although IL6R remained elevated, β2 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.