Researcher Investigates How Mother’s Diet Shapes Liver Health

OKLAHOMA CITY – University of Oklahoma researcher Keenan Greyslak, Ph.D., has long been interested in how a mother’s diet during pregnancy and lactation may influence a child’s risk of developing metabolic diseases earlier and more severely as they age. With a new grant from the National Institutes of Health, he is furthering his investigations while taking another step toward a career in academic biomedical research.

Greyslak is a postdoctoral fellow at the OU College of Medicine, working in the laboratory of Jed Friedman, Ph.D., a professor in the college, director of the OU Health Harold Hamm Diabetes Center and Associate Vice Provost for Diabetes Programs on the OU Health Campus. The new grant, called an F32, is designed not only to advance research but to enhance the training of fellows who have the potential to become independently funded investigators. With the new grant, Greyslak seeks to better understand how a mother’s high-fat, high-sugar diet can predispose her child to conditions like metabolic-associated steatotic liver disease (MASLD), a buildup of fat that can progress to inflammation and scarring in the liver.

“Children born to mothers with poor nutrition or obesity appear to have immune cells that are more prone to inflammation,” he said, “and we are learning more and more that inflammation is linked to many chronic diseases. So, these children are starting off already at risk for diseases like MASLD.”

Greyslak’s research focuses on mitochondria, the tiny energy-producing structures inside cells that also help control immune cell behavior. He is investigating whether a mother’s high-fat, high-sugar diet changes mitochondrial function during early development, causing macrophages – immune cells that normally help fight infection and repair damaged tissue – to remain in an inflammatory state instead of helping the liver heal. Over time, that chronic inflammation may contribute to liver damage and scarring.

In this project, Greyslak will feed female mice a typical American-style diet, high in fat and sugar, before and during pregnancy and/or lactation. He will then examine how the offspring’s immune cell mitochondria impact inflammation in response to maternal diet at these different stages of development. Specifically, he will examine the livers and immune cells of these offspring as juveniles and young adults.

“MASLD has traditionally been considered a disease of adults, affecting an estimated 30% to 40% of the population, largely driven by the obesity epidemic,” Friedman said. “Alarmingly, it is now recognized in approximately one-third of children with obesity and nearly 10% of all adolescents. Why this disease is emerging so early in life remains poorly understood, highlighting an urgent need to identify the biological mechanisms that drive pediatric MASLD and develop strategies to prevent it.”

People with MASLD also face a higher risk of developing metabolic-associated steatohepatitis (MASH), a more severe form of liver disease that can cause permanent liver damage, increase the risk of liver cancer and eventually require a liver transplant.

As part of the project, Greyslak is working closely with OU Health physicians who care for children as young as 8 or 9 years old with MASLD, some already showing signs of liver scarring. This clinical perspective is important, he said, for understanding how his laboratory work translates to changes happening in these children and young adolescents. He also hopes to identify therapeutic targets and strategies that benefit these at-risk pediatric patients beginning in early life and into adulthood and beyond.

“Even if a child (exposed to poor maternal nutrition in early life) later eats a healthy diet … our research suggests that changes to mitochondrial function may not be reversible,” Greyslak said. “Ultimately, we want to design a way to intervene before these changes become permanent.”

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About the project

Research reported in this release is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number F32DK146538-01.

About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and healthcare needs of the state, region and nation. In Oklahoma City, the OU Health Campus is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. The OU Health Campus serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about the OU Health Campus, visit www.ouhsc.edu.