BOSTON — The in utero environment in obese mothers may program a child’s cells to accumulate extra fat or develop differences in metabolism that could lead to insulin resistance, according to a new study presented at the American Diabetes Association (ADA) 75th Scientific Sessions.

These changes could, in part, explain why children of obese parents are prone to obesity themselves, placing them at a higher risk for type 2 diabetes.

“We know from large population-based studies that obesity during pregnancy is considered an important risk factor for increased infant adiposity at birth, as well as for increased risk of obesity and metabolic disease in later life,” said study investigator Kristen Boyle, PhD, who is an assistant professor of pediatrics at the University of Colorado School of Medicine in Aurora. 

“We did this study to better understand how this occurs. We found that mesenchymal stem cells derived from umbilical cord tissue of babies born to obese mothers had greater potential to become fat cells than those derived from umbilical cord of babies born to normal weight mothers.”

Boyle and her team took stem cells from donated umbilical cords of the babies of normal-weight and obese mothers and grew them into fat and muscle cells in the lab. The investigators tested whether mesenchymal stem cells (MSCs) derived from umbilical cord tissue of babies born to obese mothers would exhibit increased adipogenesis and decreased myogenesis in culture. The team also looked for evidence of insulin resistance when differentiated to myocytes.  

The MSCs were cultured from term infants (39 weeks) born to 12 obese mothers. The mean pre-pregnancy BMI was 35.1. These women were compared with 12 normal-weight mothers with a mean BMI of 21.2. Prior to differentiation, MSCs of obese mothers expressed two-fold greater CD13, a cell surface marker linked with increased adipogenesis.

The researchers found a 30% higher fat content in fat and muscle cells grown in culture in the offspring of mothers who were obese at their first prenatal visit, as compared with the cells of offspring of normal-weight mothers.

Boyle said because these findings are fairly preliminary, it is still unknown how these differences in cells grown in the lab correspond to the physiology of these children after birth. However, she said it’s clear that there is an inherent propensity toward more fat content in the cells from offspring of obese mothers in culture.   

“The fat content in these cells corresponded to infant fat mass at birth, which suggests that the capacity for fat cell development in vitro may reflect in vivo development of fat mass. We will continue to follow these children so that we can gain better insight into whether measures in the stem cells correspond to outcomes in the children as they grow,” explained Boyle.

The researchers expect to soon have additional information on how the cells use fat for energy production and whether this contributes to the greater fat accumulation in the cells from the offspring of obese mothers. They are continuing to conduct a full, metabolic assessment of the cells to determine whether the cells in the offspring of obese moms display inflammation, insulin resistance or other metabolic differences.

“At this time, there are no immediate clinical implications for this research. But eventually, if we can use this stem cell model to gain insight into how pregnancy obesity exposures affect fetal development and metabolic disease risk, we may be able to design intervention programs to mitigate adverse effects in the offspring,” Boyle told Endocrinology Advisor.

Reference

  1. Boyle KE et al. Abstract 381-OR: Human Mesenchymal Stem Cells from Offspring of Obese Mothers Have Increased Adipogenesis and Evidence for Insulin Resistance: The Healthy Heart Study. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.