Maternal Serum Metabolomics in Mid-Pregnancy Identifies Lipid Pathways as a Key Link to Offspring Obesity in Early Childhood.

Autor: Francis EC; Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA., Kechris K; Department of Biostatistics & Informatics, Colorado School of Public Health, Aurora, CO 80045, USA., Johnson RK; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Rawal S; Department of Clinical and Preventive Nutrition Sciences, School of Health Professions, Rutgers University, Newark, NJ 07102, USA., Pathmasiri W; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Rushing BR; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Du X; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA., Jansson T; Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Dabelea D; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; The Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Sumner SJ; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Perng W; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; The Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Jul 11; Vol. 25 (14). Date of Electronic Publication: 2024 Jul 11.
DOI: 10.3390/ijms25147620
Abstrakt: Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference ( n = 360); High HDL-C ( n = 289); Dyslipidemic-High TG ( n = 149); Dyslipidemic-High FFA ( n = 180); Insulin Resistant (IR)-Hyperglycemic ( n = 87). These subgroups not only captured metabolic heterogeneity among pregnant participants but were also associated with offspring obesity in early childhood, even among women without obesity or diabetes. Here, we utilize metabolomics data to enrich characterization of the metabolic subgroups and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 pregnant women at 18 gestational weeks using untargeted metabolomics. We used weighted gene correlation network analysis (WGCNA) to derive a global network based on the Reference subgroup and characterized distinct metabolite modules representative of the different metabolomic profiles. We used the mummichog algorithm for pathway enrichment and identified key compounds that differed across the subgroups. Eight metabolite modules representing pathways such as the carnitine-acylcarnitine translocase system, fatty acid biosynthesis and activation, and glycerophospholipid metabolism were identified. A module that included 189 compounds related to DHA peroxidation, oxidative stress, and sex hormone biosynthesis was elevated in the Insulin Resistant-Hyperglycemic vs. the Reference subgroup. This module was positively correlated with total cholesterol (R:0.10; p -value < 0.0001) and free fatty acids (R:0.07; p -value < 0.05). Oxidative stress and inflammatory pathways may underlie insulin resistance during pregnancy, even below clinical diabetes thresholds. These findings highlight potential therapeutic targets and strategies for pregnancy risk stratification and reveal mechanisms underlying the developmental origins of metabolic disease risk.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje