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.

• This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

Creator

• Sibley, Katelyne Jean

Publisher

• Worcester Polytechnic Institute

Identifier

• E-project-032518-140108

Advisor

• Gericke, Arne

Year

• 2018

Sponsor

• UMass Medical School

Date created

• 2018-03-25

Resource type

• Major Qualifying Project

Major

• Biochemistry

Rights statement

• In Copyright