Laboratory of Cell Biology, Institute of Life Sciences, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
J Nutr Biochem. 2011 Oct;22(10):985-94. doi: 10.1016/j.jnutbio.2010.08.015. Epub 2010 Dec 28.
Accumulating evidence has shown that maternal malnutrition increases the risk of metabolic disease in the progeny. We previously reported that prenatal exposure to a low-protein diet (LP) leads to mitochondrial dysfunction in pancreatic islets from adult rodent offspring that could relate physiological and cellular alterations due to early diet. We aim to determine whether mitochondrial dysfunction could be a common consequence of prenatal nutritional unbalances. Pregnant Wistar rats received either a global food restriction (GFR), consisting in the reduction by 50% of the normal daily food intake, or a high-fat diet (HF) throughout gestation. GFR or HF diet during pregnancy leads to a lack of increase in insulin release and ATP content in response to glucose stimulation in islets from 3-month-old male and female offspring. These similar consequences originated from impairment in either glucose sensing or glucose metabolism, depending on the type of early malnutrition and on the sex of the progeny. Indeed, the glucose transport across β-cell membrane seemed compromised in female HF offspring, since GLUT-2 gene was markedly underexpressed. Additionally, for each progeny, consequences downstream the entry of glucose were also apparent. Expression of genes involved in glycolysis, TCA cycle and oxidative phosphorylations was altered in GFR and HF rats in a sex- and diet-dependent manner. Moreover, prenatal malnutrition affected the regulators of mitochondrial biogenesis, namely, PPAR coactivator 1 alpha (PGC-1α), since its expression was higher in islets from GFR rats. In conclusion, programming of mitochondrial dysfunction is a consequence of maternal malnutrition, which may predispose to glucose intolerance in the adult offspring.
越来越多的证据表明，母体营养不良会增加后代患代谢性疾病的风险。我们之前曾报道，产前暴露于低蛋白饮食（LP）会导致成年啮齿动物后代胰岛中的线粒体功能障碍，这可能与早期饮食引起的生理和细胞变化有关。我们旨在确定线粒体功能障碍是否是产前营养失衡的共同后果。怀孕的 Wistar 大鼠在整个孕期接受全面的食物限制（GFR），即正常每日食物摄入量减少 50%，或高脂肪饮食（HF）。孕期 GFR 或 HF 饮食会导致 3 个月大的雄性和雌性后代胰岛对葡萄糖刺激的胰岛素释放和 ATP 含量增加不足。这些相似的后果源于葡萄糖感应或葡萄糖代谢的损伤，这取决于早期营养不良的类型和后代的性别。事实上，HF 饮食的雌性后代的β细胞葡萄糖跨膜转运似乎受损，因为 GLUT-2 基因明显表达不足。此外，对于每个后代，葡萄糖进入后的下游后果也很明显。在 GFR 和 HF 大鼠中，糖酵解、三羧酸循环和氧化磷酸化相关基因的表达也以性别和饮食依赖的方式发生改变。此外，产前营养不良还会影响线粒体生物发生的调节因子，即过氧化物酶体增殖物激活受体共激活因子 1α（PGC-1α），因为 GFR 大鼠胰岛中的 PGC-1α 表达更高。总之，线粒体功能障碍的编程是母体营养不良的后果，这可能使成年后代易患葡萄糖耐量受损。
