Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome.
Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome.
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DOI：
10.2337/db10-1239
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发表时间：
2011-02
期刊：
影响因子：
7.7
通讯作者：
Davidge ST
中科院分区：
文献类型：
--
作者：
Rueda-Clausen CF;Dolinsky VW;Morton JS;Proctor SD;Dyck JR;Davidge ST
人们认识到，对高脂肪（HF）饮食的全身反应存在显着的变异性，这不能完全用遗传因素来解释。此外，导致宫内生长受限（IUGR）的妊娠并发症与日后患代谢综合征（MetS）的风险增加有关。因此，我们假设出生时患有 IUGR 的后代表现出永久性的代谢变化，使他们更容易受到 HF 饮食诱导的 MetS 的影响。出生时正常（对照）或缺氧诱导的 IUGR 的 SD 大鼠被随机分为低脂（10% 脂肪）或 HF（45% 脂肪）饮食。喂养 9 周后，对 MetS 涉及的生理和分子途径进行了评估。与对照组相比，IUGR 后代表现出能量摄入和体力活动减少。在饲喂HF饮食的后代中，IUGR与全身脂肪含量降低、腹内脂肪沉积和脂肪细胞大小相对增加、瘦素、甘油三酯和游离脂肪酸空腹血浆浓度增加以及肝脏和骨骼肌中甘油三酯和神经酰胺浓度增加有关。脂质稳态的这些变化伴随着体内胰岛素抵抗和葡萄糖耐量受损，并与肝脏和骨骼肌中对胰岛素响应的蛋白激酶 C θ 磷酸化增加、胰岛素受体底物 1 抑制以及蛋白激酶 B (PKB；也称为 Akt) 活化减少相关。 IUGR 会增强对 HF 饮食的特定有害代谢反应。我们的结果表明，出生时患有 IUGR 的后代可能需要特别关注和随访，以防止 MetS 过早发病。
It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet–induced MetS. SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated. IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C θ, inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin. IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS.