Uncovering a Link Between Liver Fat and Fibrosis
PhD Candidate Naideline Raymond, working with thesis mentors Michael Czech, PhD, and Batuhan Yenilmez, PhD published new findings in a bioRxiv preprint that reveal how a common form of fatty liver disease progresses from a manageable condition to one that causes lasting liver damage—and how that process might be stopped.
Their studies focus on a liver enzyme called HSD17B13, which influences how the liver stores fat. This new investigation showed the enzyme does more than handle fat. When it is overly active, it sends signals that trigger liver scarring, known as fibrosis. They pinpointed a key messenger, TGF-β1 (transforming growth factor beta-1), as the link between liver fat buildup and the activation of scar-forming cells.
In people born with a less active version of the HSD17B13 gene, those harmful signals are reduced, protecting them from severe liver disease. This discovery offers a biological explanation for genetic studies showing these individuals are less likely to develop cirrhosis.
“This work connects two major pieces of the metabolic disease puzzle,” said Dr. Czech, the Isadore & Fannie Foxman Chair of Medical Research in the Program in Molecular Medicine. “It explains how excess fat inside liver cells can trigger the scarring process that causes lasting damage.”
Dr. Yenilmez, Assistant Professor in the Program in Molecular Medicine, stated that, “These new results also provide us with a new approach to learn even more about the underlying mechanisms of how different cell types communicate within the liver.”
The findings align closely with the collaborators’ mission to uncover how genes and proteins control metabolism and identify therapeutic targets for obesity, type 2 diabetes, and related disorders. Studying insulin signaling in fat and muscle to exploring organ-to-organ communication, they aim to translate molecular discoveries into therapies that restore metabolic balance. This newly published data adds a vital liver-focused piece to that mission.
By discovering safe ways to reduce HSD17B13 activity or block its TGF-β1 signaling, scientists may be able to prevent liver scarring before it becomes irreversible—a significant step toward treating the root causes of fatty liver disease and other metabolic disorders.
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