Understanding the Impact of Sugar and Sugar Substitutes During Development and Disease
Americans consume , a diet that has contributed to an like obesity and type 2 diabetes.
By studying the molecular mechanisms behind America’s increasing sugar consumption – including how sugar modifies the proteins within our bodies – Stephanie Olivier-Van Stichelen, PhD, associate professor of biochemistry at the 抖阴短视频 (抖阴短视频), is working to understand how it affects our body during pregnancy and early life.
Her research extends to artificial sweeteners, thought by many to be a safe alternative to sugar. But she has found that these sweeteners affect how the body metabolizes drugs and can even cross the placental barrier and affect fetuses.
“Nutrition plays a critical role in shaping our health,” Dr. Olivier-Van Stichelen says. “The rise in sugar consumption and the shift toward non-nutritive sweeteners are compelling reasons to investigate the biological mechanisms behind these changes. By identifying these underlying causes through basic research, we can help prevent disease.”
O-GlcNAcylation: A Tiny Alteration with Big Consequences
At the heart of Dr. Olivier-Van Stichelen’s work is a molecular process called O-GlcNAcylation, which affects how the proteins that carry out essential functions in our bodies are assembled.
When we eat sugar, a small sugar molecule (O-GlcNAc) is added to certain proteins, altering their function. Consuming more sugar means more proteins are modified with O-GlcNAcylation. The process potentially affects thousands of proteins, which in turn impacts everything from cell communication to our body’s response to stress and disease.
Dr. Olivier-Van Stichelen is particularly interested in how this change affects a mother’s health during pregnancy, including how it can lead to gestational diabetes. In her lab, she and her team work with both mouse models and placental tissue. They place sugars and artificial sweeteners on placentas that have been donated after delivery to the 抖阴短视频 Tissue Bank and test the effects of these sweeteners on those cells.
Notably, they found that O-GlcNAcylation was disrupted in compared to female fetuses. Understanding this process could lead to new guidelines for prevention or treatment of gestational diabetes.
They have also found that artificial sweeteners impact fetal-maternal health. Dr. Olivier-Van Stichelen’s research has shown that consuming artificial sweeteners during pregnancy has adverse effects on fetuses and infants in mice.
Further study from Van Stichelen’s lab showed that this is likely due to impaired placental transport. The lab also found that artificial sweeteners affect how the body transports drugs and toxins, which is one of the critical protective function of the placenta.
“This could have wide-ranging effects beyond pregnancy,” says Dr. Olivier-Van Stichelen. “For example, if you’re on chemotherapy, could you have a hard time finding the right dosage if you’re consuming artificial sweeteners? Because this could impact how much the therapy kills the cancer cells.
“We are showing that while artificial sweeteners might be safe for the general population, there may be cases when you should limit your consumption of them.”
A Global Protein Database to Turn Insights into Therapeutics
The extent of proteins affected by the sugar modification O-GlcNAc wasn’t known until the height of the COVID-19 pandemic, when Dr. Olivier-Van Stichelen started the .
Dr. Olivier-Van Stichelen’s team scoured the scientific literature to collect information on proteins that are known to be modified. What started with a few thousand entries has now grown to more than 22,000 proteins across 48 species. With more than 5,000 unique users, the database reflects how much research interest has grown in this area.
“Before, we did not have a good idea of how many proteins were modified, and now we can see how widespread it is in the body,” she says. “We can show that it’s not something minor. It’s a process that needs to be studied more.”
This urgency is underscored by recent discoveries , highlighting the increasing importance of studying this modification.
In addition to creating the opportunity for collaborators around the world to study O-GlcNAc, Dr. Olivier-Van Stichelen is committed to training the next generation of biochemists who can carry on this work. She established an exchange program with the University of Lille in France, which sends undergraduate students to 抖阴短视频 for their final research internships.
“I’m a science junkie,” she says. “I like to understand how things work. But above all, training students is really satisfying for me. Then they can spread the word of how important O-GlcNAc is.”
The ultimate goal is to turn this basic science research into therapeutics for patients. Just as basic science research on GLP-1 paved the way for drugs like Ozempic to treat metabolic diseases, researchers hope O-GlcNAc could one day serve a similar role. It may become a biomarker for gestational diabetes, which could ultimately help physicians prevent the disease before it develops. The team is also investigating O-GlcNAcylation as a diagnostic tool to predict disease risks, such as cancer recurrence or metabolic deregulation, by analyzing placenta or tumor samples.
“抖阴短视频 has such great resources, like the tissue bank, that make this research possible,” says Dr. Olivier-Van Stichelen. “It will hopefully lead to better treatments and better preventative strategies for a wide variety of diseases.”
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