‘Tiny Messengers Orchestrate Metabolism’

Janos Zempleni portrait
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‘Tiny Messengers Orchestrate Metabolism’

Nebraska Center for Obesity Prevention and Dietary Molecules focuses on science of human health.

Interview with Janos Zempleni by Bryce Doeschot

Each time a person takes a drink of milk or a bite of food, nanoparticles – known as exosomes – within the milk or food deliver signals to different tissues in the human body that can turn genes on and off during the body’s normal metabolic function. The result of this gene activity can lead to life-changing diseases, but scientists are learning to change the effect of the exosomes and hopefully, prevent human disease.

Janos Zempleni, Willa Cather Professor of Molecular Nutrition in the Department of Nutrition and Health Sciences at the University of Nebraska–Lincoln, also is director of the Nebraska Center for Obesity Prevention and Dietary Molecules (NPOD). Zempleni and a team of more than 50 university researchers work with nutrigenomics and computational sciences to solve complex problems by studying exosomes in food. 

The objective of NPOD is to prevent obesity-related diseases, Zempleni said, by finding answers to complex questions about the human body. The current research focus areas are non-alcoholic
fatty liver disease, heart disease, obesity and nutrient signaling.

The center, which began in 2014 with an $11.3 million grant funded by National Institutes of Health, is located at the university and collaborates with the University of Nebraska Medical Center. 

Long-term, Zempleni would like to develop consumer-friendly pathways that improve health, without major disruptions in people’s lives. He expects the university and NPOD to become a leader in nutrient signaling, controlling the genes that affect disease.

COMPLEX RESEARCH

Exosomes are nanoparticles that are not visible to the eye. One exosome contains as many as 10,000 different compounds. The exosomes are found in foods, including liquids such as milk. They control how tissues communicate with each other. The NPOD research team studies exosomes to find answers to complex problems within the human body, detecting diseases such as cancer. 

 “The exosomes deliver these signals to all kinds of tissues in our bodies and turn on and turn off genes,” Zempleni said. “They’re tiny messengers that orchestrate the metabolism. They regulate all 25,000 genes that a human has, and they affect different tissues in different ways.”

Zempleni said one research project involved animal feeding studies, looking at excessive intake or depletion of exosomes in the animals’ diet. One of the changes was in the DNA building blocks produced in animals. The team began studying the diets of human babies to determine what effect the animals’ diet had on the infants.

“We observed that breast milk versus cow’s milk formula versus soy formula had very different levels of exosome cargoes, which would have major implications for infants fed formulas,” Zempleni said. A study was begun that collected urine samples from equal numbers of infants consuming breast milk, cow’s milk formula and soy formula. Although the study is still being conducted, Zempleni said there is a different pattern of DNA building blocks in the urine of the infants fed cow’s milk or soy formula versus the pattern of breastfed infants. “This is one of the examples where animal studies actually translate nicely into human research,” he added.

DATA COLLABORATIONS

One of the many challenges of exosome research is that it generates huge data sets, Zempleni said, and these large data sets must be analyzed. “There has been a spike in data generation, of big data in our lab because of all the exosome work and the thousands of genes that these exosomes affect,” he said.

Zempleni defines “big data” as anything that requires more than a desktop or laptop computer for processing the data. 

“The data sets are huge. We generate the data in the lab in collaboration with biochemistry or other institutions in the United States,” Zempleni said. The data becomes such a large part of the laboratory that students and staff are dedicated to handling the data. 

Zempleni and his research team build computational expertise within their research group by including graduate students with strengths in data analysis, as well as collaborators from other departments. Juan Cui, an assistant professor in the Department of Computer Science and Engineering, is such a collaborator. Cui’s research is in understanding human disease through data integration and computer modelling.

“We create this data and ask all the biology questions, and then Dr. Cui comes in and applies her magic – does the analysis of the data – and she comes up with system solutions,” Zempleni said. 

SOLUTIONS

“People can no longer spend their entire research career looking at one single pathway,” Zempleni said. Now, there are complex systems and patterns that have created a whole-systems approach. He believes that is where data science has advanced the field of biology. 

“We are trying to change the way biologists work with computational scientists or data specialists,” Zempleni said. “In reality, we still talk a different language: they ‘talk computer,’ we ‘talk biology.’ Sometimes it’s impossible to really understand what the other party is talking about and that is one of the things we want to solve.” In the case of the NPOD group, Zempleni arranges joint lab meetings so the computational partners learn about biology and the biology partners learn about computer data analysis. 

HEALTHIER FOOD

By understanding the research on exosomes and DNA makeup, Zempleni and his team research ways to make food healthier for people, to the point that using food for medicine can be part of the future. 

Zempleni is not a big believer in dietary supplements, especially when it comes to supplements for individual nutrients. Many of these supplements cannot be used by the body, he said, because they are above the limit of what a person can absorb. Instead, Zempleni says that a balanced nutrition has major impact on a healthy lifestyle and disease prevention. 

Beyond consumer choice, researchers at the center can begin to change the way food is composed to make it healthier. 

Although it is possible to change the nutrient composition, Zempleni says that switching from saturated fatty acid, like butter, to olive oils can make dramatic differences in a person’s health. “It’s not about the amount of fat you consume, but the type of fat that you consume,” Zempleni said. “We can tweak the pathways in plants or in animals to actually produce more of these healthy fatty acids,” Zempleni said.

“We can tweak the nutrient composition in foods to make them healthier,” Zempleni said. “That’s really the future – this breeding for biomedical traits.”