Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, California, USA.
Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
JCI Insight. 2024 Sep 3;9(19):e180016. doi: 10.1172/jci.insight.180016.
Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis in vitro, we used lipidomics to distinguish phenotypes by unbiased cluster analysis and lipid challenge (24-hour excess fatty acid [24hFA]). We measured MSC AMP-activated protein kinase (AMPK) activity and fatty acid oxidation (FAO), and a composite index of maternal glucose, insulin, triglycerides, free fatty acids, TNF-α, and high-density lipoprotein and total cholesterol in fasting blood from mid and late gestation (~17 and ~27 weeks, respectively). We measured child adiposity at birth (n = 29), 4-6 months (n = 29), and 4-6 years (n = 13). Three MSC clusters were distinguished by triacylglycerol (TAG) stores, with greatest TAGs in Cluster 2. All clusters increased acylcarnitines and TAGs with 24hFA, although Cluster 2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC clusters and child adiposity at 4-6 years (both highest in Cluster 3). Our data support the notion that MSC phenotypes are predicted by comprehensive maternal metabolic milieu exposures, independent of maternal BMI, and suggest utility as an at-birth predictor for child adiposity, although validation with larger longitudinal samples is warranted.
我们的目的是探究间充质干细胞（MSC）的脂质代谢以及母体体重以外的妊娠暴露因素，这些因素可能会增加儿童肥胖的风险。我们从肥胖（n=16）或正常体重（n=15）产妇的足月婴儿中培养 MSC。在体外成肌细胞分化过程中，我们采用脂质组学通过无偏聚类分析和脂质刺激（24 小时过量脂肪酸（24hFA））来区分表型。我们测量了 MSC 腺苷酸活化蛋白激酶（AMPK）活性和脂肪酸氧化（FAO），以及妊娠中期（约 17 周）和晚期（约 27 周）空腹血中母体葡萄糖、胰岛素、甘油三酯、游离脂肪酸、TNF-α、高密度脂蛋白和总胆固醇的综合指数。我们测量了出生时（n=29）、4-6 个月（n=29）和 4-6 岁（n=13）时儿童的肥胖程度。通过三酰基甘油（TAG）储存，区分出三个 MSC 簇，其中簇 2 的 TAG 最多。所有簇均随着 24hFA 的增加而增加酰基肉碱和 TAG，尽管簇 2 的变化更为明显，与 AMPK 激活和 FAO 相对应。母体代谢标志物可预测 MSC 簇和儿童 4-6 岁时的肥胖程度（簇 3 的最高）。我们的数据支持这样一种观点，即 MSC 表型由母体代谢环境的综合暴露来预测，而与母体 BMI 无关，并表明其作为出生时预测儿童肥胖的指标具有一定的应用价值，但需要更大的纵向样本进行验证。
