Yamada Makiko, Wolfe Diana, Han Guang, French Samuel W, Ross Michael G, Desai Mina
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, USA.
Congenit Anom (Kyoto). 2011 Dec;51(4):167-73. doi: 10.1111/j.1741-4520.2011.00336.x.
Intrauterine growth-restricted (IUGR) newborns have increased risk of adult metabolic syndrome, including fatty liver. However, it is unclear whether the fatty liver development is "programmed" or secondary to the accompanying obesity. In this study, we examined hepatic lipid accumulation and lipid-regulatory factors (sterol regulatory element-binding protein-1c and fatty acid synthase) in IUGR and Control fetal (embryonic day 20; e20) and newborn (postnatal day 1; p1) rat pups. Notably, despite of in utero undernutrition state, IUGR fetuses demonstrated "fatty liver" with upregulation of these lipogenic indices at as early as e20. Both IUGR and Control newborns exhibited the same extent of massive increase in hepatic lipid content, whereas IUGR newborns continued to exhibit upregulated lipogenic indices. The persistent upregulation of the lipogenic indices in fetal and newborn IUGR suggests that fatty liver is gestationally programmed. Our study suggested that IUGR offspring were born with an altered metabolic life strategy of increased fuel/lipid storage which could be a distinct metabolic pathway of the thrifty phenotype.
宫内生长受限（IUGR）新生儿患成人代谢综合征（包括脂肪肝）的风险增加。然而，尚不清楚脂肪肝的发展是“程序化的”还是继发于伴随的肥胖。在本研究中，我们检测了IUGR和对照胎鼠（胚胎第20天；e20）及新生鼠（出生后第1天；p1）肝脏中的脂质蓄积及脂质调节因子（固醇调节元件结合蛋白-1c和脂肪酸合酶）。值得注意的是，尽管处于宫内营养不足状态，但IUGR胎儿早在e20时就表现出“脂肪肝”，且这些生脂指标上调。IUGR和对照新生鼠肝脏脂质含量均出现相同程度的大幅增加，而IUGR新生鼠的生脂指标持续上调。胎儿和新生IUGR生脂指标的持续上调表明脂肪肝是在孕期程序化的。我们的研究表明，IUGR后代出生时具有改变的代谢生活策略，即增加燃料/脂质储存，这可能是节俭表型的一种独特代谢途径。
