Choi Gyu Yeon, Tosh Darran N, Garg Ambica, Mansano Roy, Ross Michael G, Desai Mina
Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA, USA.
Am J Obstet Gynecol. 2007 May;196(5):477.e1-7. doi: 10.1016/j.ajog.2007.02.024.
Intrauterine growth restriction demonstrates increased risk of adult metabolic syndrome. The associated hyperlipidemia results from obesity or programmed metabolic abnormalities. Because lipid homeostasis is regulated by the liver, we hypothesized that hepatic structure and lipid content in intrauterine growth restriction would reflect a primary lipid dysfunction.
From 10 days to term gestation, control pregnant rats received ad libitum diet; study rats were 25% food-restricted (FR). All dams received ad libitum diet throughout lactation. At 3 weeks of age, hepatic lobule size and lipid profile of the pups were determined.
At 3 weeks of age, body and liver weights of the pups were comparable with controls, although with reduced hepatic lobule size. FR males had increased hepatic triglyceride and cholesterol content with elevated sterol regulatory element-binding protein-1c, fatty acid synthase, and lipoprotein lipase expression; FR females exhibited decreased hepatic cholesterol levels. Plasma lipid levels were unchanged in FR males and females.
Developmental programming results in sex-dependent altered lipid metabolism with increased risk in males.
宫内生长受限显示出成人代谢综合征风险增加。相关的高脂血症是由肥胖或程序化代谢异常引起的。由于脂质稳态由肝脏调节，我们推测宫内生长受限中的肝脏结构和脂质含量会反映原发性脂质功能障碍。
从妊娠第10天到足月，对照孕鼠自由饮食；研究鼠进行25%的饮食限制（FR）。所有母鼠在整个哺乳期自由饮食。在幼鼠3周龄时，测定其肝小叶大小和脂质谱。
在3周龄时，幼鼠的体重和肝脏重量与对照组相当，尽管肝小叶大小减小。FR雄性幼鼠肝脏甘油三酯和胆固醇含量增加，固醇调节元件结合蛋白-1c、脂肪酸合酶和脂蛋白脂肪酶表达升高；FR雌性幼鼠肝脏胆固醇水平降低。FR雄性和雌性幼鼠的血浆脂质水平未发生变化。
发育程序化导致性别依赖性脂质代谢改变，雄性风险增加。
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