Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

ABSTRACT: Huntington's disease arises from a toxic gain of function in the huntingtin (HTT) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcrip

SUBMITTER: Bragg RM 

PROVIDER: S-EPMC10488683 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature