Researchers at the University of Colorado Anschutz’s Linda Crnic Institute for Down Syndrome have unveiled significant findings linking liver dysfunction in individuals with Down syndrome to dietary factors. The study, published in Cell Reports, highlights elevated levels of bile acids and other liver dysfunction biomarkers in this population, suggesting that dietary modifications could improve health outcomes.
The research identifies unique liver dysfunction in those with Down syndrome, a condition that affects the liver’s vital functions, including detoxification, metabolism, and immunity. Through a comprehensive multiomic analysis of plasma samples from over 400 participants in the Human Trisome Project, researchers noted consistent elevations in bile acids, independent of body mass index or other health conditions.
Understanding Liver Dysfunction in Down Syndrome
The liver’s role in producing bile, metabolizing nutrients, and supporting immune function is critical, and disruptions can have widespread health effects. The study demonstrated that hepatocytes, the liver’s most abundant cells, derived from induced pluripotent stem cells from individuals with Down syndrome, show intrinsic metabolic dysfunction. This includes altered bile acid production and excessive fat storage, pointing to a genetic basis for these abnormalities.
To further explore these mechanisms, researchers utilized the Dp16 mouse model, which shares many genetic characteristics with Down syndrome. These mice exhibited liver abnormalities such as inflammation and fibrosis, similar to those seen in humans with Down syndrome. Notably, dietary fat intake significantly influenced these outcomes, with high-fat diets exacerbating liver injury, while low-fat diets mitigated the effects.
“Our data show that Down syndrome profoundly impacts hepatic metabolism,” said Kelly Sullivan, PhD, senior author and associate professor of Pediatrics at the University of Colorado Anschutz. “Importantly, we found that dietary fat intake can exacerbate or ameliorate these effects in the mouse models, suggesting that nutrition could play a key role in managing liver health in this population.”
The Role of Diet in Managing Liver Health
This research underscores the importance of dietary strategies in managing liver health in individuals with Down syndrome. Liver disease affects millions in the U.S., yet its prevalence in Down syndrome has been poorly understood until now. The study’s findings emphasize the need for early monitoring and dietary interventions to reduce risk.
Joaquín Espinosa, PhD, executive director of the Crnic Institute, highlighted the significance of this research.
“The fact that liver dysfunction had not been well documented in this population until now highlights the value of transformative research funding through the National Institutes of Health INCLUDE Project and the Global Down Syndrome Foundation.”
Michelle Sie Whitten, president & CEO of the Global Down Syndrome Foundation, expressed gratitude for the research’s potential impact.
“With additional research in this area, we hope that more detailed information on diet and other treatments will help my 22-year-old daughter and millions of others with Down syndrome to live longer, healthier lives.”
Future Directions and Implications
The research team plans to explore clinical interventions, including low-fat diets and lifestyle modifications, to assess their impact on liver health in individuals with Down syndrome. This approach could lead to practical interventions that significantly improve liver and overall health in this population.
The Linda Crnic Institute for Down Syndrome, a leader in Down syndrome research, continues to drive scientific discovery through advanced biomedical research. Supported by the Global Down Syndrome Foundation and other partners, the institute is committed to improving the lives of those with Down syndrome through innovative research and collaboration.
The University of Colorado Anschutz Medical Campus, home to the Crnic Institute, is a hub of transformative advances in science and medicine. With substantial funding and renowned research, the campus plays a pivotal role in developing life-changing treatments and exceptional patient care.
The Global Down Syndrome Foundation remains at the forefront of advocacy and research, supporting scientists and patients worldwide. Through its initiatives and partnerships, GLOBAL aims to enhance health outcomes and quality of life for individuals with Down syndrome.
