Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring.
Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring.
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母体蛋白质限制诱导成年大鼠后代肝肿瘤坏死因子-α/CYP7A1信号的改变和胆固醇代谢的调节紊乱
DOI：
10.3164/jcbn.13-100
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发表时间：
2014-07
影响因子：
2.4
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Liu X;Qi Y;Tian B;Chen D;Gao H;Xi C;Xing Y;Yuan Z
众所周知，宫内不良事件损害胎儿发育，并导致成年后肥胖和代谢综合征的发展。胆固醇升高是代谢综合征和心血管疾病的重要临床危险因素，为探讨胆固醇升高与胎儿生长发育不良的关系，我们采用蛋白质限制模型检测了母亲营养不良对子代肝脏肿瘤坏死因子-α（TNF-α）/c-jun N-末端激酶（JNK）信号通路和胆固醇7α-羟化酶（CYP 7A 1）表达的影响。由等热量低蛋白饮食引起的宫内生长受限（IUGR）的雄性后代在出生时表现出肝脏重量下降，40周龄时循环和肝脏胆固醇水平增加。从胎龄到成年，母亲营养不良显著上调肝脏中细胞因子TNF-α表达和JNK磷酸化水平。JNK磷酸化水平升高可能与肝细胞核因子-4 α和CYP 7A 1表达下调有关，随后导致肝脏胆固醇升高。本研究表明，宫内营养不良导致的IUGR可能导致肝脏TNF-α/CYP 7A 1信号转导的内在紊乱，并在以后的生活中促进高胆固醇血症的发展。
It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-α (TNF-α)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7α-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-α expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4α and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-α/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life.
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影响因子：
3.3
作者：
Bagley HN;Wang Y;Campbell MS;Yu X;Lane RH;Joss-Moore LA
通讯作者：
Joss-Moore LA
子宫内生长限制下调肝脏 Toll 样受体 4 的表达和功能。
影响因子：
--
作者：
Equils, Ozlem;Singh, Sapna;Karaburun, Semra;Lu, Daning;Thamotharan, Manikkavasagar;Devaskar, Sherin U
通讯作者：
Devaskar, Sherin U
母体蛋白质限制诱导宫内生长受限胎鼠下丘脑胰岛素信号和 ATP 敏感钾通道蛋白的改变
影响因子：
2.4
作者：
Liu X;Qi Y;Gao H;Jiao Y;Gu H;Miao J;Yuan Z
通讯作者：
Yuan Z
影响因子：
3.2
作者：
Faienza, Maria Felicia;Brunetti, Giacomina;Cavallo, Luciano
通讯作者：
Cavallo, Luciano
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR