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New model allows for analysis of fetal fat tissue

In vivo model of fat tissue growth could aid understanding of childhood obesity

A new model in mice, developed by University researchers, could aid the understanding of human fat tissue growth in fetuses.

In the study, published in the Journal of Lipid Research Sept. 5, the researchers transplanted the living fat tissue of human fetuses into mice, where the tissue grew in vivo. They then monitored factors affecting the rate and type of the tissue growth, a process that could eventually aid the understanding of the development of obesity, said Jennifer Sanders, assistant professor of pediatrics and co-author of the paper.

The animal model the researchers created, using a method called xenotransplantation, is the first to sustain human fetal adipose tissue growth in vivo. Previously, only cell cultures outside of living bodies were used to study fat tissue growth. Now, the new model offers a much more realistic view of tissue growth, said co-author Philip Gruppuso, professor of pediatrics and molecular biology, cell biology and biochemistry.

“This presented an opportunity to study human fetal tissue growth in vivo, and you can’t do that any other way,” Gruppuso said.

Future research could use this model to better understand the fetal basis of adult obesity and diseases such as diabetes, Sanders said. There is epidemiological evidence showing that factors inside the womb affect the eventual outcome of obesity, she said.

The researchers plan to analyze the histology and cell types present in the model at several time points during the tissue’s growth, she added.

“We were taken back by how much this tissue grew,” much more than researchers initially expected, Gruppuso said. The tissue was taken from stillbirths at Women and Infants Hospital that were 18 to 22 weeks in gestation.

The most immediate applicability of this model is in the field of epigenetics, Gruppuso said. By changing the DNA transcription and translation in the tissue, researchers can gain an understanding of how fetal genes affect fat tissue growth throughout the human lifespan, he added.

The model provides “a new front for the community to investigate cell biology, differentiation and development of (fat tissue cells) in human(s) as well as in animals,” wrote Zhihua Jiang, an associate professor of animal sciences at Washington State University who was not involved with the study, in an email to The Herald.

The project was a “major collaborative effort,” involving several labs and institutions, Gruppuso said.

Though this model provides motivation for future pathology research, there are known limitations to using a non-human model, Gruppuso said. A mouse model does not perfectly model human fat tissue growth, and an immune response cannot be seen or studied because the mice are immuno-compromised.

But the experimental design still has much to offer, Sanders said. “Hopefully other labs will adopt this model.”


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