Ying Chen, PhD

Alexander M. White, III Postdoctoral Research Fellowship Award
$25,000 over one year

Baylor College of Medicine

Spatiotemporal regulation of lipid metabolism in MAFLD

Mentor: Dongyin Guan, PhD Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing health concern that can lead to more severe liver issues like inflammation (MASH), fibrosis, and liver cancer. The livers zonation, where distinct hepatocyte populations perform specific functions, contributes to the diversity of these roles. In advanced stages of MAFLD, damage patterns vary by liver zone. Circadian rhythms, which cycle approximately every 24 hours, also influence liver function and help maintain health by adapting to daily changes. Misalignment of these rhythms can lead to lipid-related metabolic diseases. However, the interplay between liver zonation and circadian rhythms in regulating lipid metabolism in MAFLD is still unclear. Our research aims to explore how lipid metabolism in the liver is regulated spatially by different regions of liver cells and temporally by circadian rhythms. We have identified a protein, estrogen-related receptor gamma (ESRRγ), that plays a crucial role in coordinating fat metabolism in alignment with the liver’s daily rhythms. In MAFLD, ESRRγ activity increases, particularly in specific liver regions, potentially influencing fat processing. We will use advancedgenetic techniques in mouse models to study how the removal of ESRRγ in certain liver cells affects fat buildup and overall liver health. Additionally, we will test whether activating ESRRγ at specific times of the day can slow or prevent liver damage. By understanding how lipid metabolism is regulated across different areas of the liver and at different times, we hope to identify new strategies for treating MAFLD. Our goal is to develop targeted, time-based therapies that leverage the liver s natural rhythms to improve fat metabolism and prevent disease progression.