High-Fat Intake During Pregnancy and Lactation Exacerbates High-Fat Diet-Induced Complications in Male Offspring in Mice
High-Fat Intake During Pregnancy and Lactation Exacerbates High-Fat Diet-Induced Complications in Male Offspring in Mice
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DOI：
10.1210/en.2012-1877
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发表时间：
2013-10-01
期刊：
影响因子：
4.8
通讯作者：
Charron, Maureen J.
中科院分区：
文献类型：
--
作者：
Kruse, Michael;Seki, Yoshinori;Charron, Maureen J.
胎儿环境的改变，例如高脂肪环境，会导致后代代谢异常。不同的产后环境揭示了胎儿时期发生的成人疾病的易感性。本研究调查了断奶后 23 周食用正常食物后，母亲高脂肪饮食 (HFD) 对后代再次接触 HFD 的代谢反应的能力。野生型 CD1 雌性在怀孕和哺乳期间喂食 HFD (H) 或对照 (C) 食物。在 26 周龄时，后代要么再次暴露 (H-C-H) 要么新暴露 (C-C-H) HFD 19 周。每周测量体重，并在 HFD 10 周和 18 周后测量葡萄糖和胰岛素耐量。妊娠期和哺乳期采用 HFD 或 C 饮食的后代与 26 周时断奶采用低脂饮食的后代的代谢情况相似。与 C-C-H 相比，在晚年重新引入 HFD 后，H-C-H 后代的体重增加了更多，并且形成了更大的脂肪细胞。 H-C-H 小鼠葡萄糖和胰岛素不耐受，肌肉中 cox6a2 和 atp5i 基因表达降低，表明线粒体功能障碍。在脂肪细胞中，与 C-C-C 小鼠相比，H-C-H 小鼠中 slc2a4、srebf1 和 adipoq 基因的表达降低，表明胰岛素抵抗。与 C-C-H 相比，H-C-H 显示广泛的肝脂肪变性，并伴有 cd36 和 serpin1 基因表达增加。围产期接触 HFD 会导致小鼠在以后的生活中对 HFD 挑战产生更有害的反应，即使是在正常饮食一段时间后。
Altered fetal environments, such as a high-fat milieu, induce metabolic abnormalities in offspring. Different postnatal environments reveal the predisposition for adult diseases that occur during the fetal period. This study investigates the ability of a maternal high-fat diet (HFD) to program metabolic responses to HFD reexposure in offspring after consuming normal chow for 23 weeks after weaning. Wild-type CD1 females were fed a HFD (H) or control (C) chow during pregnancy and lactation. At 26 weeks of age, offspring were either reexposed (H-C-H) or newly exposed (C-C-H) to the HFD for 19 weeks. Body weight was measured weekly, and glucose and insulin tolerance were measured after 10 and 18 weeks on the HFD. The metabolic profile of offspring on a HFD or C diet during pregnancy and lactation and weaned onto a low-fat diet was similar at 26 weeks. H-C-H offspring gained more weight and developed larger adipocytes after being reintroduced to the HFD later in life than C-C-H. H-C-H mice were glucose and insulin intolerant and showed reduced gene expression of cox6a2 and atp5i in muscle, indicating mitochondrial dysfunction. In adipocytes, the expression of slc2a4, srebf1, and adipoq genes was decreased in H-C-H mice compared with C-C-C, indicating insulin resistance. H-C-H showed extensive hepatosteatosis, accompanied by increased gene expression for cd36 and serpin1, compared with C-C-H. Perinatal exposure to a HFD programs a more deleterious response to a HFD challenge later in life even after an interval of normal diet in mice.