Federal Project Grant Award Summary

The University of Texas Southwestern Medical Center has received a $676,279 project grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective January 15, 2026 through November 30, 2029. This award funds basic biomedical research aimed at identifying metabolic regulators of hepatic phosphatidylcholine (PC) synthesis and their relationship to metabolic dysfunction-associated fatty liver disease (MAFLD). The research focuses on characterizing the role of the transmembrane oxidoreductase VKORC1L1 in regulating hepatic PC levels and preventing hepatic fat accumulation, utilizing liver-specific knockout and overexpression mouse models under varying dietary conditions to assess impacts on very-low-density lipoprotein (VLDL) secretion, hepatic lipid accumulation, and whole-body metabolic health.

The project delivers fundamental research outputs that advance understanding of disease mechanisms underlying MAFLD, a condition affecting over 25% of the U.S. population, with potential applications for improved prevention and treatment strategies. The research investigates how VKORC1L1 influences the three major pathways maintaining PC levels—the Kennedy pathway, phosphatidylethanolamine methylation, and lipid salvage—and explores the connection between human VKORC1L1 variants and liver steatosis, thereby contributing to the NIDDK program's objective to improve understanding of digestive and metabolic diseases through investigator-initiated biomedical research.