Magee Thomas R, Han Guang, Cherian Bindu, Khorram Omid, Ross Michael G, Desai Mina
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Am J Obstet Gynecol. 2008 Sep;199(3):271.e1-5. doi: 10.1016/j.ajog.2008.05.022. Epub 2008 Jul 29.
Intrauterine growth-restricted (IUGR) newborns 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 C-reactive protein (CRP) levels were analyzed in 1 day and 9 month old male offspring.
At 1 day of age, IUGR pups showed down-regulation of PPARalpha and PPARgamma and up-regulation of hepatic lipase and CRP. At 9 months of age, IUGR exhibited continued down-regulation of PPARalpha and PPARgamma with up-regulation of sterol regulatory element-binding protein-1 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.
宫内生长受限（IUGR）新生儿患肥胖诱导性脂肪肝和炎症的风险增加。我们推测，IUGR诱导的肝脏过氧化物酶体增殖物激活受体（PPARs）抑制与炎症反应增加有关。
对照母鼠随意进食，而研究母鼠从妊娠第10天至21天食物限制50%（IUGR）。幼崽由对照母鼠哺乳并断奶后随意进食。对1日龄和9月龄雄性后代的肝脏转录因子蛋白表达、脂质酶、甘油三酯含量和C反应蛋白（CRP）水平进行分析。
1日龄时，IUGR幼崽表现出PPARα和PPARγ下调，肝脂肪酶和CRP上调。9月龄时，IUGR表现出PPARα和PPARγ持续下调，固醇调节元件结合蛋白-1和脂肪酸合酶上调。此外，IUGR成年鼠肝脏甘油三酯含量和血浆CRP水平升高。
结果表明，发育性肝脏调节异常可能导致IUGR后代出现程序性肥胖诱导的炎症。
