Public Release: 

High-fat diet, obesity during pregnancy harms stem cells in developing fetus

Findings may provide broad context for the rise in immune disease and allergic disposition in children

Oregon Health & Science University

PORTLAND, Ore. -- Physician-scientists at OHSU Doernbecher Children's Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function.

The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The findings are published in the journal Molecular Metabolism.

"Our results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations," said Daniel L. Marks, M.D., Ph.D., co-investigator and professor of pediatric endocrinology in the OHSU School of Medicine and Papé Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Several years ago, Marks and colleagues developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver.

Armed with this information, Marks partnered with another stem cell expert, Peter Kurre, M.D., co-investigator on the current study and professor of pediatric oncology in the OHSU School of Medicine and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Together, they discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system.

"In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system," Kurre said. "These findings may provide broad context for the rise in immune disease and allergic disposition in children."

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The study, "Maternal high-fat diet and obesity compromise fetal hematopoiesis," was funded by Friends of Doernbecher and by the Oregon Clinical Translational Research Institute at OHSU. Research reported in this press release] was supported by National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128

Kurre and Marks also are members of the OHSU Knight Cancer Institute and Oregon Stem Cell Center at OHSU.

OHSU researchers who contributed to this research include: Kurre, Marks, Ashley N. Kamimae-Lanning, Stephanie M. Krasnow, Natalya A. Goloviznina, Xinxia Zhu, Quinn R. Roth-Carter, Peter R. Levasseur, Sophia Jeng, Shannon K. McWeeney.

ABOUT OHSU DOERNBECHER CHILDREN'S HOSPITAL

OHSU Doernbecher Children's Hospital ranks among the nation's Best Children's Hospitals,* is one of 21 members of the Children's Oncology Group's Phase 1 and Pilot Consortium, and ranks 39th for NIH awards to children's hospitals and their university-affiliated Department of Pediatrics.** Nationally recognized physicians and nurses provide a full range of specialty and subspecialty care to tens of thousands of children annually, resulting in 200,000 discharges, surgeries, transports and outpatient visits annually in a patient- and family-centered environment. OHSU Doernbecher providers also travel throughout Oregon and Southwest Washington, providing specialty care to more than 3,000 children at more than 200 outreach clinics in 15 locations. Using state-of-the-art, secure two-way video and audio communication, OHSU Doernbecher's Telemedicine Network connects pediatric intensivists and neonatologists to emergency room physicians statewide to help evaluate time-critical pediatric patient needs and assist with treatment plans.

* U.S. News & World Report 2014-15 Best Children's Hospitals

** Children's Hospital Association

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