Mitochondrial inefficiency in infants born to overweight African-American mothers

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.

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.

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.

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.