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Transcriptomic Analysis of Neonatal Lamb Hearts After Maternal Hypercortisolemia Suggests Altered Triglyceride Synthesis
Author(s) -
Richards Elaine,
Antolic Andrew,
Wood Charles,
KellerWood Maureen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.684.2
Subject(s) - medicine , endocrinology , insulin resistance , offspring , triglyceride , fetus , biology , downregulation and upregulation , insulin , pregnancy , cholesterol , gene , biochemistry , genetics
Our previous studies using a sheep model of maternal stress showed that 15 days of a maternal 1mg/kg/day infusion of cortisol to 130‐days of a 145‐day gestation caused hyperplastic fetal hearts with Purkinje fiber apoptosis while treatment to term resulted in significantly increased perinatal fetal death. Fetuses collected before death had deranged expression of genes regulating cardiac metabolism and decreased mitochondria. To study effects of increased maternal cortisol on lambs we infused 8 ewes with saline (CON) and 8 with 0.5mg/kg/day cortisol (CORT) until parturition, the lambs' hearts were collected at age 14‐days for transcriptomic analyses of the septa using 1‐color Agilent ovine 8x15k microarrays. Differentially expressed genes were determined by Jmp genomics, with pathway inference by Webgestalt and Cytoscape. qPCR validated some findings. CORT lambs had larger LV wall thickness/tibia ratios, 0.496 + 0.007 vs 0.445 + 0.006. 228 genes were down‐ and 263 upregulated in CORT vs CON. Modeling the upregulated genes suggested that CORT affected mitochondrial membranes and endoplasmic reticulum, the location of diacylglycerol O‐acyl transferase 2 (DGAT2). DGAT2 expression was significantly increased in CORT (fold change 1.05 + 0.13 vs 2.97 + 0.58, p<0.05). DGAT2 synthesizes triglycerides de novo from glycerol‐3‐phosphate and increases insulin resistance in glycolytic muscle fibers (Levi et al Am. J. Physiol. Endocrinol. Metab. 2007, 293: E1772). DGAT1 expression was not changed. Thus maternal stress may predispose the offspring to cardiomyopathy due to increased triglyceride deposition.