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Offspring of obese mothers may be pre-programmed for metabolic disease
BOSTON — Mesenchymal stem cells from the offspring of mothers with obesity may be programmed in utero to accumulate extra fat before birth, putting those children at an increased risk for obesity and metabolic disease, according to study findings presented here.
In a longitudinal study involving umbilical cord mesenchymal stem cell (MSC) cultures from mothers with obesity and normal weight, researchers found that, in mothers with obesity, the in utero environment may program their offspring’s tissues to accumulate excess fat compared with mothers in the normal-weight range.
“We know that children born to [mothers with obesity] have an increased risk of becoming obese and developing metabolic disease later in life, including type 2 diabetes,” Kristen E. Boyle, PhD, an assistant professor at the University of Colorado School of Medicine, said in a press conference announcing the study findings. “But we don’t really understand exactly how this occurs.”
Boyle and colleagues analyzed data from the stem cells of 24 full-term infants; 15 born to mothers in a normal-weight range (mean age, 28 years; pre-pregnancy BMI, 21 kg/m2) and 14 born to mothers with obesity (mean age, 28 years; pre-pregnancy BMI, 35 kg/m2) participating in the Healthy Start Study, a longitudinal, pre-birth cohort of 1,410 mother–infant dyads. Researchers cultured MSCs from infants in both study arms.
Before differentiation, MSCs from the infants of mothers with obesity expressed twofold greater CD13, a cell surface marker linked to increased adipogenesis (P < .05).
MSCs were then differentiated to either adipocytes (fat cells) or myocytes (muscle cells) for 21 days. Researchers also measured the protein markers of adipogenesis (peroxisome proliferator-activated receptor [PPAR] gamma) and myogenesis (myosin heavy chain [MHC]). Researchers stained cells with oil red O (ORO) to assess lipid accumulation.
When differentiated to fat cells, MSCs from mothers with obesity expressed 50% more PPAR-gamma protein content than MSCs from mothers of normal-weight range (P < .05). When the MSCs were differentiated to muscle cells, there were no differences in MHC content, although ORO staining indicated a 50% higher lipid content in the MSCs of infants of mothers with obesity (P < .05).
“Once we grew [the stem cells] into fat cells in the lab, we see that the [cells] from [mothers with obesity] have a greater fat accumulation and they have higher content of markers of fat cells, which would indicate that they have a greater propensity to become fat cells,” Boyle said. “Also, we noticed that the fat accumulation in these cells corresponded to the fat mass of the babies when they were born.”
In addition, when researchers grew MSCs into muscle cells, they discovered the ability to oxidize fats was lower in the offspring of the mothers with obesity, she said.
“These results give us insight into how obesity and pregnancy may impact the growth of the baby in utero, which could eventually give us insight into how certain children born to obese mothers may have increased risk for developing metabolic disease or obesity later in life,” Boyle said.
She said researchers hope to follow the cohort to observe whether there is a lasting change into adulthood. – by Regina Schaffer
Reference:
Boyle KE, et al. Abstract 381-OR. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.
Disclosure: The researchers report no relevant financial disclosures.