Prenatal metabolomic profiles mediate the effect of maternal obesity on early childhood growth trajectories and obesity risk: the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study

被引:4
作者
Hu, Zunsong [1 ]
Han, Luhang [1 ]
Liu, Jiawang [2 ,3 ]
Fowke, Jay H. [1 ]
Han, Joan C. [4 ,5 ,6 ,7 ]
Kakhniashvili, David [8 ]
LeWinn, Kaja Z. [9 ]
Bush, Nicole R. [9 ,10 ]
Mason, W. Alex [1 ]
Zhao, Qi [1 ]
机构
[1] Univ Tennessee, Coll Med, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA
[2] Univ Tennessee, Off Res, Med Chem Core, Hlth Sci Ctr, Memphis, TN USA
[3] Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Hlth Sci Ctr, Memphis, TN USA
[4] Univ Tennessee, Dept Pediat, Hlth Sci Ctr, Memphis, TN USA
[5] Univ Tennessee, Dept Physiol, Hlth Sci Ctr, Memphis, TN USA
[6] Le Bonheur Childrens Hosp, Childrens Fdn Res Inst, Memphis, TN USA
[7] Icahn Sch Med Mt Sinai, Kravis Childrens Hosp, New York, NY 10029 USA
[8] Univ Tennessee, Hlth Sci Ctr, Prote & Metabol Core, Off Res, Memphis, TN USA
[9] Univ Calif San Francisco, Weill Inst Neurosci, Dept Psychiat & Behav Sci, San Francisco, CA 94143 USA
[10] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
关键词
childhood obesity; growth trajectory; maternal obesity; mediation; metabolomics; BODY-MASS INDEX; MENDELIAN RANDOMIZATION; OXIDATIVE STRESS; WEIGHT-GAIN; HEALTH; OVERWEIGHT; WOMEN;
D O I
10.1093/ajcn/nqac244
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Background Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. Objectives The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. Methods We included 450 African-American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study pregnancy cohort. LC-MS was used to conduct metabolomic profiling on maternal plasma samples of the second trimester. The childhood growth outcomes of interest included BMI trajectories from birth to age 4 y (rising-high-, moderate-, and low-BMI trajectories) as well as overweight/obesity (OWO) risk at age 4 y. Mediation analysis was conducted to identify metabolite mediators linking maternal OWO and childhood growth outcomes. The potential causal effects of maternal OWO on metabolite mediators were examined using the Mendelian randomization (MR) method. Results Among the 880 metabolites detected in the maternal plasma during pregnancy, 14 and 11 metabolites significantly mediated the effects of maternal prepregnancy OWO on childhood BMI trajectories and the OWO risk at age 4 y, respectively, and 5 mediated both outcomes. The MR analysis suggested 6 of the 20 prenatal metabolite mediators might be causally influenced by maternal prepregnancy OWO, most of which are from the pathways related to the metabolism of amino acids (hydroxyasparagine, glutamate, and homocitrulline), sterols (campesterol), and nucleotides (N2,N2-dimethylguanosine). Conclusions Our study provides further evidence that prenatal metabolomic profiles might mediate the effect of maternal OWO on early childhood growth trajectories and OWO risk in offspring. The metabolic pathways, including identified metabolite mediators, might provide novel intervention targets for preventing the intrauterine development of obesity in the offspring of mothers with obesity.
引用
收藏
页码:1343 / 1353
页数:11
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