Research examines how maternal obesity reprograms babies

Research examines how maternal obesity reprograms babies

Research increasingly suggests that when a woman with obesity becomes pregnant, a process of "fetal reprogramming" increases the risk that her baby will face problems such as obesity, type 2 diabetes and liver disease earlier in life.

To better understand how this reprogramming occurs, researchers at the University of Oklahoma recently received a $2.3 million grant from the National Institutes of Health. They will also study whether an antioxidant called PQQ given to the mother can reduce the risk of future metabolic problems for her offspring.

“Today, more than 40% of women of childbearing age in the United States are overweight or obese,” said Karen Jonscher, Ph.D., a researcher at the OU College of Medicine who, along with Dean Myers, Ph., leads the grant’s work. D. "Research has shown that people whose mothers were obese during pregnancy have a higher risk of developing metabolic dysfunction-associated steatotic liver disease, a fatty liver disease that progressively worsens and may require transplantation. However, this is the case in offspring." happens earlier in life and with more serious problems. The entire process appears to be accelerated in children born to mothers with obesity.

Much of America's obesity problem is attributed to a high-fat "Western" diet. However, even if a woman with obesity eats healthier during pregnancy, her offspring are still at higher risk of disease. Jonscher and Myers believe the key may lie in what happens in the placenta -; the interface between mother and fetus.

Obesity is essentially a low-grade, chronic inflammatory disease. Fat cells cause inflammation, which means the body's white blood cells are constantly activated and can damage other cells and tissues. Cholesterol and triglyceride levels rise and blood pressure rises. Jonscher theorizes that inflammation in pregnant women with obesity causes the placenta to send a signal to the fetus's stem cells, telling it to reprogram itself to become more vulnerable to the damaging effects of inflammation.

There is even evidence that inflammation changes the way nutrients are transported to the fetus, so that fat is preferentially transported rather than the building blocks of proteins.”

Karen Jonscher, Ph.D., associate professor of biochemistry and physiology, College of Medicine, University of Oklahoma

With the grant, Jonscher and Myers will attempt to prove this hypothesis. Additionally, they will test an antioxidant called pyrroloquinoline quinone (PQQ) for its ability to block or reverse fetal reprogramming. PQQ is found in fruits and vegetables and has anti-inflammatory properties. However, if a person does not eat a healthy diet, they are less likely to have adequate levels of PQQ.

In their preliminary studies in a preclinical research model, the researchers found that giving PQQ to overweight mothers protected their offspring from fatty liver disease in adulthood. Because women are generally discouraged from taking weight loss medications during pregnancy because they could harm the fetus, researchers hope that PQQ is both safe and effective.

“Based on the data we have collected so far, we believe PQQ will result in a healthier pregnancy,” Myers said. "The mother may still have a high body mass index, but PQQ appears to be able to reduce inflammation and improve cholesterol and lipid levels. If we can improve the mother's health, we also improve the function of the placenta, which protects the fetus." And if we can protect the placenta, nutrient transport will be improved as more amino acids and protein building blocks reach the fetus instead of fats, as well as better oxygen flow.”

Myers, a professor in the Department of Obstetrics and Gynecology, often speaks with his clinical colleagues who care for women with obesity during their pregnancy. Exercising and eating healthy can be difficult for everyone, pregnant or not, and doctors need another tool to help women become metabolically healthier during pregnancy.

“Our goal is to create a less inflamed and healthier placenta,” he said. "Hopefully PQQ will also help the mother, as pregnant women with obesity are at increased risk of gestational diabetes. If our research with this grant is successful, we hope to move PQQ into clinical trials in a few years."

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