母鼠高脂饮食致子代大鼠胰岛素抵抗的研究

Maternal High-fat Diet Exposure Leads to Insulin Resistance and Impacts Skeletal Muscle and Adipose Tissue Gene Expression in Offspring-rats

研究母鼠高脂饮食导致子代大鼠产生胰岛素抵抗(IR)的机制,包括母体高脂饮食摄入造成子代大鼠发育编程异常和成年后的代谢疾病,以及对子代大鼠骨骼肌和脂肪组织发育相关基因的影响。将雌性SD大鼠随机分为2组,NC组喂以标准饲料,高脂组喂以高脂饲料,整个过程监控动物体质量、生化指标、口服糖耐量(OGTT)并计算胰岛素敏感指数(ISI)。与正常雄鼠交配后,繁殖子鼠按性别和母鼠来源分为4组:正常雌性组、正常雄性组、高脂雌性组和高脂雄性组。子代大鼠断奶后喂以标准饲料18周,同样监控体质量、生化指标、OGTT和ISI。处死动物后,获取股四头肌并观察其细胞核和线粒体形态。另外检测子代大鼠在胚胎和胎儿阶段的脂肪和肌肉发育的基因表达情况。结果表明:高脂母鼠及其子鼠显示出明显的IR症状,而母鼠高脂饮食摄入使子鼠在胚胎胎儿阶段的脂肪和肌肉发育的基因表达受到严重干扰。研究结果说明,高脂的宫内环境可能通过影响脂肪和肌肉发育导致子鼠产生IR。

To explore the molecular mechanisms of insulin resistance （IR） in offspring-rats under maternal high-fat diet exposure, we investigated whether maternal high-fat diet consumption can result in offspring malprogramming and the onset of metabolic diseases in adulthood, and can impact skeletal muscle and adipose tissue gene expression. Sprague-Dawley female rats were randomly divided into two groups and fed either a normal rodent chow （NC） or high-fat diet （HF）. The body weights of the rats were monitored and plasma parameters, oral glucose tolerance test （OGTT）, insulin sensitivity index （ISI） were measured. After mating with normal adult male rats, the pups of HF and NC female rats were divided into four groups according to dams and gender： male offspring of maternal HF （MOH）, female offspring of maternal HF （FOH）, male offspring of maternal NC （MON） and female offspring of maternal NC （FON）, Offspring-rats were fed NC until 18 weeks after weaning and weighed weekly. Plasma parameters, OGTT and IS/of offspring-rats were obtained and the morphology of nuclei and mitochondria from left quadriceps ceils in offspring-rats was observed. During the embryonic and fetal period, the expression of 10 marker genes related to adipogenesis and myogenesis was detected. The results showed that maternal high-fat diet exposure revealed obvious IR in MOH and FOH. The expression of adipogenetic and myogenetic genes was disrupted seriously in MOH and FOH. As a consequence, maternal high-fat diet exposure leads to IR in offspring rats through impacting the expression of adipogenetic and myogenetic genes.