Supplement: Administrative Supplements for Research on Sexual and Gender Minority (SGM) Populations

In this Administrative Supplements for Research on Sexual and Gender Minority Populations, our aim is to fill a significant gap in Turner syndrome (TS) research by addressing how the missing sex chromosome impacts liver health in this unique female population. Patients with TS frequently present with obesity and liver damage, including non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are unclear. Leveraging our expertise in NAFLD study, this application focuses on investigating the role of an X-linked gene, KDM6a/UTX, in TS-associated NAFLD. KDM6a/UTX, a gene that codes for H3K27 demethylases, is downregulated in TS patients as well as in TS mouse livers. It plays a critical role in the histone demethylation of genes crucial for heart development and is also associated with the development of hyperinsulinemia, metabolic abnormalities, or acetaminophen overdose-induced hepatotoxicity. Based on these findings, we hypothesize that KDM6a/UTX may play a role in the development of Turner syndrome-related NAFLD. This hypothesis will be tested by both in vitro and in vivo studies, involving the utilization of primary mouse hepatocytes and Turner syndrome mouse models. The successful completion of these studies will establish whether KDM6a is a key player in regulating hepatocyte lipid metabolism and fatty liver disease in Turner Syndrome mouse models. This will lay a critical foundation for future translational studies contributing to the well-being of Turner Syndrome patients.