Down-regulation of transcription factor peroxisome proliferator-activated receptor in programmed hepatic lipid dysregulation and inflammation in intrauterine growth-restricted offspring.
Down-regulation of transcription factor peroxisome proliferator-activated receptor in programmed hepatic lipid dysregulation and inflammation in intrauterine growth-restricted offspring.
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DOI：
10.1016/j.ajog.2008.05.022
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发表时间：
2008-09
影响因子：
9.8
通讯作者：
Desai, Mina
中科院分区：
文献类型：
--
作者：
Magee, Thomas R.;Han, Guang;Cherian, Bindu;Khorram, Omid;Ross, Michael G.;Desai, Mina
关键词：
宫内生长受限新生儿（IUGR）会增加肥胖引起的“脂肪肝”和炎症的风险。我们假设 IUGR 诱导的肝过氧化物酶体增殖物激活受体 (PPAR) 抑制与炎症反应增加有关。大鼠对照母鼠随意进食，而研究母鼠从怀孕第 10 天到第 21 天 (IUGR) 限制 50% 的食物。幼崽由对照母鼠喂养并断奶后自由采食。分析 1 日龄和 9 月龄雄性后代的肝蛋白表达、转录因子、脂质酶、甘油三酯含量和 CRP 水平。 1天龄时，IUGR幼仔表现出PPARγ和PPARα下调，肝脂肪酶和CRP上调。 9 个月大时，IUGR 表现出 PPARγ 和 PPARα 持续下调，同时 SREBP1 和脂肪酸合酶上调。此外，IUGR 成人的肝脏甘油三酯含量和血浆 CRP 水平升高。结果表明，发育性肝脏失调可能导致 IUGR 后代出现程序性肥胖引起的炎症。
Intrauterine growth restricted newborns (IUGR) have increased risk of obesity-induced “fatty liver” and inflammation. We hypothesized that IUGR-induced inhibition of hepatic peroxisome proliferator activated receptors (PPARs) is associated with an increased inflammatory response. Rat Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (IUGR). Pups were nursed by Control dams and weaned to ad libitum feed. Hepatic protein expression of transcription factors, lipid enzymes, triglyceride content and CRP levels were analyzed in 1 day and 9 month old male offspring. At 1d of age, IUGR pups showed downregulation of PPARγ and PPARα, upregulation of hepatic lipase and CRP. At 9 months of age, IUGR exhibited continued downregulation of PPARγ and PPARα with upregulation of SREBP1 and fatty acid synthase. Furthermore, IUGR adults had increased hepatic triglyceride content and plasma CRP levels. The results suggest that developmental hepatic dysregulation may contribute to programmed obesity-induced inflammation in IUGR offspring.
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