Faculty Advisor

Gericke, Arne

Center

UMMC / University of Massachusetts Medical Center

Abstract

PRMT5’s regulation of SREBP1 expression in hepatocytes was investigated in the context of NAFLD. Depleting PRMT5 expression by shRNA mediated gene silencing or inhibiting its enzymatic activity by a small molecule inhibitor decreased SREBP1 expression on mRNA and protein levels. There is no change on its direct target genes involved in de novo lipogenesis. PRMT5 knockdown or inhibition reduced the PI3K-AKT signaling pathway, in which the expression of genes involved in mitochondrial biogenesis was significantly enhanced. As a consequence of PRMT5 inhibition, lipid droplet accumulation was decreased in the presence of a PRMT5 inhibitor. The results indicate that PRMT5 regulates hepatic lipid homeostasis independent of SREBP1 and that PRMT5 inhibitor could have beneficial effects on NAFLD.

Publisher

Worcester Polytechnic Institute

Date Accepted

March 2018

Major

Biochemistry

Project Type

Major Qualifying Project

Accessibility

Unrestricted

Advisor Department

Chemistry and Biochemistry

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