Lipid droplet screen in human hepatocytes identifies TRRAP as a regulator of cellular triglyceride metabolism.
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
29
09
2020
accepted:
08
12
2020
pubmed:
23
6
2021
medline:
15
2
2022
entrez:
22
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34156146
doi: 10.1111/cts.12988
pmc: PMC8301584
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Nuclear Proteins
0
Triglycerides
0
transformation-transcription domain-associated protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1369-1379Subventions
Organisme : Pilot Grant
ID : HTSC-15-003-01
Organisme : Seymour Grey
Informations de copyright
© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
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