Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring.
Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring.
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DOI：
10.1371/journal.pone.0189977
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ford SP
中科院分区：
文献类型：
--
作者：
Ghnenis AB;Odhiambo JF;McCormick RJ;Nathanielsz PW;Ford SP
人类孕期肥胖使后代在出生后易患肥胖症和心血管疾病。在母体营养过剩/肥胖的绵羊模型中，我们先前报告了晚期胎儿的心肌炎症和纤维化以及心功能障碍，并与慢性血皮质醇升高有关。重大研究表明，宫内糖皮质激素暴露增加与出生后高血压和心血管疾病之间存在联系。在这里，我们研究了母亲肥胖对其成年后代心肌炎症和纤维化的影响。对照组(CON)的成年雄性后代喂养100%的国家研究委员会(NRC)建议(n=6)，肥胖母亲(MO)的雄性后代喂养150%的NRC(n=6)，接受为期12周的自由喂养挑战，然后解剖。在尸检时，成年雄性MO子代血浆皮质醇和左、右室厚度显著增加(P<；0.05)。与CON子代相比，MO子代的心肌胶原含量和胶原交联度更高(P<；0.05)，并且与糖皮质激素受体(GR)的mRNA和蛋白表达增加有关。心肌盐皮质激素受体(MR)蛋白表达差异无统计学意义。促炎症细胞因子CD-68、转化生长因子-β-1和肿瘤坏死因子-α的基因表达增加(P<0.05)，CD-68、转化生长因子-β-1和肿瘤坏死因子-α的蛋白表达有增加的趋势(P<0.05)。这些数据为MO诱导的成年子代血浆皮质醇升高和心肌炎症和纤维化提供了证据，可能是通过增加GR。
Obesity during human pregnancy predisposes offspring to obesity and cardiovascular disease in postnatal life. In a sheep model of maternal overnutrition/obesity we have previously reported myocardial inflammation and fibrosis, as well as cardiac dysfunction in late term fetuses, in association with chronically elevated blood cortisol. Significant research has suggested a link between elevated glucocorticoid exposure in utero and hypertension and cardiovascular disease postnatally. Here we examined the effects of maternal obesity on myocardial inflammation and fibrosis of their adult offspring. Adult male offspring from control (CON) mothers fed 100% of National Research Council (NRC) recommendations (n = 6) and male offspring from obese mothers (MO) fed 150% NRC (n = 6), were put on a 12-week ad libitum feeding challenge then necropsied. At necropsy, plasma cortisol and left and right ventricular thickness were markedly increased (P<0.05) in adult male MO offspring. Myocardial collagen content and collagen-crosslinking were greater (P<0.05) in MO offspring compared to CON offspring in association with increased mRNA and protein expression of glucocorticoid receptors (GR). No group difference was found in myocardial mineralocorticoids receptor (MR) protein expression. Further, mRNA expression for the proinflammatory cytokines: cluster of differentiation (CD)-68, transforming growth factor (TGF)-β1, and tumor necrosis factor (TNF)-α were increased (P < 0.05), and protein expression of CD-68, TGF-β1, and TNF-α tended to increase (P<0.10) in MO vs. CON offspring. These data provide evidence for MO-induced programming of elevated plasma cortisol and myocardial inflammation and fibrosis in adult offspring potentially through increased GR.
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