Two Possible Ways to Break Mother-to-Offspring Cycle of Fatty Liver Risk
Research By: Margaret Hanlon | Nikolai Timchenko, PhD
Post Date: November 14, 2023 | Publish Date: Nov. 14, 2023
Pediatric General and Thoracic Surgery | Top Scientific Achievement
Several recent studies have documented a concerning biological connection between maternal obesity, unhealthy childhood diets, and elevated risk of liver disorders in adolescents, including metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis and liver cancer.
Now a team of experts at Cincinnati Children’s has identified a crucial moment that sets up a genetic risk for obesity-related liver disease. The study was led by first author Margaret Hanlon and senior author Nikolai Timchenko, PhD.
The team conducted a large series of mouse studies that ultimately zeroed in on a mutation in the C/EBPa gene or modification of C/EBPa protein that obese women can pass along to their children during pregnancy. “We found that the phosphorylation of C/EBPa at Ser193 is a critical event,” the authors say.
C/EBPa is a master regulator protein with multiple roles in liver function. When the Ser193 mutation or Ser193 modification occur, the activities of C/EBPa change. Beyond the mouse analysis, the study reports a similar process occurring among children who show very early signs of fatty liver disease. This suggests that an early-developing phenotype precedes later liver disorders—and might be treatable.
“How can our studies be translated to humans? In mice, the most dangerous combination was a high-fat diet during pregnancy and a high-fat diet for the child. It appears that a low-fat diet after birth may reduce or eliminate the consequences of prenatal obesity in young children,” Timchenko says.
Meanwhile, CDK4 inhibitors to restrict excessive liver proliferation also might help children once they develop NASH/NAFLD. However, further studies are required to test this hypothesis.
Co-authors included Ruhi Gulati, Michael Johnston, and Yasmeen Fleifil from Cincinnati Children’s and Maria Rivas from the Institute of Biosciences, University of São Paulo.
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| Original title: | Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring |
| Published in: | Cellular and Molecular Gastroenterology and Hepatology |
| Publish date: | Nov. 14, 2023 |
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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