母代高脂饮食诱导子代在小鼠生命早期出现糖脂代谢紊乱且具有雄性易感性

目的 探讨孕期和哺乳期的高脂饮食能否导致子代在生命早期出现糖脂代谢紊乱。方法 成年雌性C57BL/6J小鼠与正常饮食雄性小鼠进行交配，孕鼠随机分为高脂饮食组和正常饮食组，在孕期和哺乳期喂养高脂饲料或正常饲料，至交配后第一代鼠断乳时（3周龄）观察其糖脂代谢相关性指标以及肝脏病理表现。结果 较正常饮食组子鼠相比，高脂饮食子鼠出生体重更低（P<0.05）。在断乳时，高脂饮食组雄性子鼠体重较重（P =0.038），腹腔糖耐量实验 30 min和60 min血糖明显升高（P值分别为<0.001和<0.01），糖耐量曲线下面积较大（P=0.0016），HOMA-IR值较大（P<0.05），雌性子鼠腹腔糖耐量实验在30 min血糖高于正常组（P<0.01），而糖耐量曲线下面积和HOMA-IR值在两组之间无明显统计学意义。雄性和雌性子代小鼠空腹胆固醇水平高脂饮食组均高于正常饮食组（P值分别为<0.0001和0.0004），而两组雄性和雌性子代小鼠空腹胰岛素和甘油三酯水平差异均无显著性（P 均>0.05）。另外，在断乳时高脂饮食子鼠出现肝脏脂肪变性，雌性和雄性子鼠无明显差异。结论 母鼠孕期和哺乳期高脂饮食能够诱导子代在生命早期就能出现糖脂代谢紊乱并且雄性子鼠更易出现肥胖、糖耐量异常、胰岛素抵抗。

Maternal high-fat diet induces aberrant glucose and lipid metabolism in the early life of offspring and male susceptibility

Objective Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat diet can induce early-onset aberrant glucose and lipid metabolism in offspring mice is less understood. Materials and Methods We examined the effects of feeding the pregnant mice with either a high fat diet or nornal chow diet throughout pregnancy and lactation on the glucose and lipid metabolism in their offsprings. Some glucose and lipid metabolism biomarkers and hepatic histology were analyzed. Results At weaning, for males of dams fed high-fat diet, they had heavier body weight, the blood glucose levels were significantly higher at 30 min (P<0.001) and 60 min (P<0.01) after intraperitoneal glucose administration, and the AUC was also significantly larger(P=0.0016) and HOMA-IR was higher(P<0.05). For females of dams fed high-fat diet, they had higher blood glucose levels at 30 min (P<0.01) after intraperitoneal glucose administration. No significant differences were observed of AUC and HOMA-IR. Both males and females of dams fed high-fat diet had elevated total cholesterol levels(P<0.0001 and P=0.0004, respectively). Triglyceride levels showed no significant differences between the two groups of males and females. The offsprings of high-fat diet group indicated hepatic steatosis and there were no differences between males and females. Conclusions Maternal high fat diet during pregnancy and lactation can induce early-onset aberrant glucose and lipid metabolism in offspring mice, and the male offsprings are more prone to metabolic changes, such as obesity, glucose intolerance and insulin resistance.