Abstract
Background
Currently 20–35% of pregnant women are obese, posing a major health risk for mother and fetus. It is postulated that an abnormal maternal-fetal nutritional environment leads to adverse metabolic programming, resulting in altered substrate metabolism in the offspring and predisposing to risks of obesity and diabetes later in life. Data indicate that oocytes from overweight animals have abnormal mitochondria. We hypothesized that maternal obesity is associated with altered mitochondrial function in healthy neonatal offspring.
Methods
Overweight and obese (body mass index, (BMI) ≥ 25 kg/m2, n = 14) and lean (BMI < 25 kg/m2, n = 8), African-American pregnant women carrying male fetuses were recruited from the Barnes Jewish Hospital obstetric clinic. Maternal and infant data were extracted from medical records. Infants underwent body composition testing in the first days of life. Circumcision skin was collected for isolation of fibroblasts. Fibroblast cells were evaluated for mitochondrial function, metabolic gene expression, nutrient uptake, and oxidative stress.
Results
Skin fibroblasts of infants born to overweight mothers had significantly higher mitochondrial respiration without a concurrent increase in ATP production, indicating mitochondrial inefficiency. These fibroblasts had higher levels of reactive oxygen species and evidence of oxidative stress. Evaluation of gene expression in offspring fibroblasts revealed altered expression of multiple genes involved in fatty acid and glucose metabolism and mitochondrial respiration in infants of overweight mothers.
Conclusions
This study demonstrates altered mitochondrial function and oxidative stress in skin fibroblasts of infants born to overweight mothers. Future studies are needed to determine the long-term impact of this finding on the metabolic health of these children.
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Acknowledgements
This project was supported by the NIH/National Center for Advancing Translational Sciences (NCATS) grant UL1 TR000448. We thank the Women’s and Infant’s Health Consortium for assistance with cord blood collection and Lana Mehanovic for help with statistical analyses. LIFE-Moms is supported by the NIH through the NIDDK (U01 DK094418, U01 DK094463, U01 DK094416, 5U01 DK094466 (RCU)), the NHLBI (U01 HL114344, U01 HL114377), the NICHD (U01 HD072834), the NCCIH, the NIH Office of Research in Women’s Health (ORWH), the Office of Behavioral and Social Science Research (OBSSR), the Indian Health Service, and the Intramural Research Program of the NIDDK. We thank the LIFE-Moms consortium members for their contributions to the development and oversight of the common measures and procedures shared across trials.
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Abraham, M., Collins, C.A., Flewelling, S. et al. Mitochondrial inefficiency in infants born to overweight African-American mothers. Int J Obes 42, 1306–1316 (2018). https://doi.org/10.1038/s41366-018-0051-z
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DOI: https://doi.org/10.1038/s41366-018-0051-z
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