"We've known for awhile that the offspring of mothers who have diabetes during pregnancy have long-term effects on development and metabolism, but more recently these findings have been extended to mothers who are obese," said Phil Zeitler, MD, PhD, a professor at the University of Colorado School of Medicine at a press conference presenting the findings here. Zeitler moderated the press conference, but was not associated with the study.
"These results indicate that the in utero environment may in fact program the offspring's tissues to accumulate excess fat," he said.
Boyle and colleagues took mesenchymal stem cells from the umbilical cords of babies with normal weight and obese mothers and grew them into fat and muscle cells in the lab. Twelve stem cells from obese mothers and 12 from normal weight mothers were cultured from the infants; all of the cells had
similar fat content at baseline.
Before the cells were cultivated and differentiated, those from obese mothers expressed two-fold greater CD13, which has been linked with increased adipogenesis, according to the study (<0.05). The cells were then cultivated as adipocytes or myocytes for 21 days and protein markers for adipogenesis and myogenesis were measured.
Researchers found that when the cells were differentiated to adipocytes, cells from babies of obese mothers expressed 50% more peroxisome proliferator-activated receptor (PPAR) protein content than did those from normal weight mothers (<0.05). And when they were differentiated to myocytes, there were no differences in myosin heavy chain (MHC) content, but cells from babies of obese mothers had a higher lipid content (P<0.05).
In addition, messenger RNA content of glucose transporter (GLUT)4 was 60% lower in the cells of babies from obese mothers, found the study. The greater lipid content and reduced GLUT4 in those cells suggest a "programmed risk for insulin resistance that may be under epigenetic control," concluded the authors.
"The cells from babies from obese moms have a greater fat accumulation and higher content of markers of fat cells, which would indicate that they have a greater propensity to become fat cells," said Boyle at the press conference. She also presented the results at an oral session here on Tuesday.
"Also, we noticed that the fat accumulation in these cells corresponded to the fat mass of the babies when they were born," she added. "The cells that accumulated more fat in the lab came from the babies that had a higher fat mass at birth."
But the results were very preliminary, according to Boyle, because it's not clear that the differences seen in the cells under the lab conditions would correspond to the physiology of the children after they are born.
"It's only be known for maybe 10-12 years that diabetes has an effect on the offspring, and then people started realizing that it's not just about diabetes, it's also about obesity," said Zeitler in an interview with MedPage Today. "People are just beginning to look into the mechanisms, so this work is really pretty early in the process."
Boyle said that they will continue to follow the children as they get older to see if they can find additional markers in the stem cells that correlate with outcomes in the children. "We're going to be measuring other metabolic outcomes in the cells, like insulin signaling, how these cells respond to treatments -- we're going to get really molecular into the pathways involved in the regulation of this," said Boyle in an interview with MedPage Today.
Researchers disclosed no relevant relationships with industry
Boyle K et al. "Human Mesenchymal Stem Cells from Offsprings of Obese Mothers Have Increased Adipogenesis and Evidence for Insulin Resistance: The Healthy Start Study" ADA 2015; 381-OR.
From www.medpageotday.com and ADA press conference
www red DiabetologNytt