Saben Jessica L, Boudoures Anna L, Asghar Zeenat, Thompson Alysha, Drury Andrea, Zhang Wendy, Chi Maggie, Cusumano Andrew, Scheaffer Suzanne, Moley Kelle H
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Cell Rep. 2016 Jun 28;16(1):1-8. doi: 10.1016/j.celrep.2016.05.065. Epub 2016 Jun 16.
Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance.
母体肥胖会损害后代健康，但其相关机制尚未完全明确。为解决这一问题，我们从受孕前至断奶期间给雌性小鼠喂食高脂/高糖饮食，然后对接下来三代后代进行跟踪观察，所有后代均喂食对照饮食。我们观察到，肥胖母亲所生的雌性后代外周胰岛素信号受损，这与线粒体功能障碍以及骨骼肌中线粒体动态和复合物蛋白改变有关。这种线粒体表型通过雌性生殖系持续存在，并遗传给第二代和第三代。我们的结果表明，代谢疾病的母体编程可通过雌性生殖系传递，异常的卵母细胞线粒体传递给后代可能会增加患胰岛素抵抗的风险。
