Lipid Droplet Screen in Human Hepatocytes Identifies TRRAP As a Regulator of Cellular Triglyceride Metabolism

Overview

Journal Clin Transl Sci

Specialties Biomedical Engineering
General Medicine

Date 2021 Jun 22

PMID 34156146

Citations 5

Authors

Deepti Abbey

Donna Conlon

Christopher Rainville

Susannah Elwyn

Katherine Quiroz-Figueroa

Jeffrey Billheimer

David C Schultz

Nicholas J Hand

Sara Cherry

Daniel J Rader

Affiliations

Soon will be listed here.

Abstract

Hepatocytes store triglycerides (TGs) in the form of lipid droplets (LDs), which are increased in hepatosteatosis. The regulation of hepatic LDs is poorly understood and new therapies to reduce hepatosteatosis are needed. We performed a siRNA kinase and phosphatase screen in HuH-7 cells using high-content automated imaging of LDs. Changes in accumulated lipids were quantified with developed pipeline that measures intensity, area, and number of LDs. Selected "hits," which reduced lipid accumulation, were further validated with other lipid and expression assays. Among several siRNAs that resulted in significantly reduced LDs, one was targeted to the nuclear adapter protein, transformation/transcription domain-associated protein (TRRAP). Knockdown of TRRAP reduced triglyceride accumulation in HuH-7 hepatocytes, in part by reducing C/EBPα-mediated de novo synthesis of TGs. These findings implicate TRRAP as a novel regulator of hepatic TG metabolism and nominate it as a potential drug target for hepatosteatosis.

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