1 CEINGE Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .
2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
Stem Cells Dev. 2018 Feb 1;27(3):199-206. doi: 10.1089/scd.2017.0198. Epub 2018 Jan 3.
Nutritional imbalance and metabolic alterations associated with maternal obesity during pregnancy predispose offspring to obesity and/or to type 2 diabetes, but the mechanisms underlying these effects are still obscure. In this context, we evaluated whether the two main energy-producing pathways (glycolysis and mitochondrial oxidative phosphorylation) are impaired in obesity during pregnancy thus contributing to metabolic intrauterine alterations. Specifically, we studied metabolic abnormalities in the intrauterine life of newborns using stem cells isolated from amnion and umbilical cord (hA- and hUC-MSCs). We isolated, at delivery, neonatal hUC-MSCs from 13 obese (Ob) and 10 normal weight control (Co) women (prepregnancy body mass index >30 and <25 kg/m, respectively) and hA-MSCs from a subgroup of 3 Ob and 3 Co women. The hUC-MSC immunophenotype was characterized by flow cytometry. The extracellular acidification rate and oxygen consumption rate, which are indicators of glycolysis and mitochondrial respiration, respectively, were measured using the Seahorse XFe96 analyzer. Basal glycolysis (Co: 27.5 ± 2.9; Ob: 21.3 ± 2.3 mpH/min) and glycolytic capacity (Co: 65.3 ± 1.2; Ob: 55.0 ± 0.3 mpH/min) were significantly lower in Ob-hUC-MSCs versus Co-hUC-MSCs (P < 0.05 and P < 0.0001, respectively). Mitochondrial basal respiration (Co: 46.9 ± 0.7; Ob: 32.6 ± 0.8 pmol/min), ATP-linked respiration (Co: 29.3 ± 1.9; Ob: 20.1 ± 0.3 pmol/min), and maximal respiration (Co: 75.2 ± 5.3; Ob: 50.5 ± 4.1 pmol/min) were significantly (P < 0.0001) lower in Ob-hUC-MSCs versus Co-hUC-MSCs. Similarly, bioenergetic profiles of the subgroup of Ob-hA-MSCs differed from those of Co-hA-MSCs. These results demonstrate that the bioenergetic performance of Ob-h-MSCs is lower in basal conditions and in conditions of increased energy demand compared with Co-h-MSCs. In conclusion, we describe a new mechanism whereby obesity alters intrauterine metabolism. This process could concur to predispose offspring to metabolic diseases in adult life.
营养失衡和代谢改变与孕期母体肥胖有关，可使后代易患肥胖症和/或 2 型糖尿病，但这些影响的机制仍不清楚。在这方面，我们评估了怀孕期间的两种主要能量产生途径（糖酵解和线粒体氧化磷酸化）是否受损，从而导致宫内代谢改变。具体来说，我们使用从羊膜和脐带中分离的干细胞（hA-和 hUC-MSCs）研究了新生儿宫内生命中的代谢异常。我们从 13 名肥胖（Ob）和 10 名正常体重对照（Co）女性（孕前体重指数 >30 和 <25kg/m）分娩时分离了新生儿 hUC-MSCs，从 3 名 Ob 和 3 名 Co 女性中分离了 hA-MSCs。通过流式细胞术对 hUC-MSC 免疫表型进行了表征。使用 Seahorse XFe96 分析仪测量分别代表糖酵解和线粒体呼吸的细胞外酸化率和耗氧量。Ob-hUC-MSCs 的基础糖酵解（Co：27.5±2.9；Ob：21.3±2.3mpH/min）和糖酵解能力（Co：65.3±1.2；Ob：55.0±0.3mpH/min）明显低于 Co-hUC-MSCs（P<0.05 和 P<0.0001）。Ob-hUC-MSCs 的线粒体基础呼吸（Co：46.9±0.7；Ob：32.6±0.8pmol/min）、ATP 连接呼吸（Co：29.3±1.9；Ob：20.1±0.3pmol/min）和最大呼吸（Co：75.2±5.3；Ob：50.5±4.1pmol/min）明显低于 Co-hUC-MSCs（P<0.0001）。同样，Ob-hA-MSCs 的生物能量谱与 Co-hA-MSCs 的生物能量谱也存在差异。这些结果表明，Ob-h-MSCs 的基础条件和能量需求增加条件下的生物能量表现均低于 Co-h-MSCs。总之，我们描述了一种新的机制，即肥胖改变了宫内代谢。这个过程可能会使后代在成年期易患代谢疾病。
