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C Wyrwoll, School of Anatomy & Human Biology, The University of Western Australia, Perth, Australia
P Mark, School of Anatomy & Human Biology, The University of Western Australia, Perth, Australia
T Mori, School of Medicine & Pharmacology, The University of Western Australia, Perth, Australia
B Waddell, School of Anatomy & Human Biology, The University of Western Australia, Perth, Australia

Correspondence: Brendan Waddell, Email: bwaddell{at}anhb.uwa.edu.au

Abstract

Fetal glucocorticoid excess programs detrimental effects in the adult phenotype including hyperleptinemia and aberrant glycemic control. In this study we determined the interactive effects of maternal dexamethasone treatment and postnatal dietary omega-3 (n-3) fatty acids on adult proinflammatory cytokine production and skeletal muscle expression of genes central to glucose handling and fatty acid metabolism. Dexamethasone acetate was administered to pregnant rats (0.75 µg/ml drinking water) from day 13 to term. Offspring of treated and control mothers were cross-fostered to mothers on either a standard or high n-3 diet, and remained on these diets post-weaning. Adult offspring exposed to dexamethasone in utero exhibited fasting hyperinsulinemia when raised on the standard diet but not when raised on the high n-3 diet. Dexamethasone also programmed increased plasma TNF and IL-1β, but the increase in IL-1β was also prevented by the high n-3 diet. In skeletal muscle, adult GLUT4 mRNA expression was elevated (up to 15-fold) after dexamethasone in utero, and this resulted in elevated intracellular, but not membrane-associated, GLUT4 protein. Fetal glucocorticoid excess also reduced adult skeletal muscle UCP3 expression in all offspring, whereas skeletal muscle expression of PPAR and PGC1 were both increased in females but not males. In conclusion, our data show that fetal glucocorticoid excess programs adult hyperinsulinemia and increased proinflammatory cytokine production. Related changes in the skeletal muscle GLUT4, UCP3 and PPAR indicate that fetal glucocorticoid excess disturbs adult glucose / fatty acid transport and metabolism.

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