Hepatic FTO expression is increased in NASH and its silencing attenuates palmitic acid-induced lipotoxicity.

Published

Journal Article

Non-alcoholic steatohepatitis (NASH) is one of the most common causes of liver failure worldwide. It is characterized by excess fat accumulation, inflammation, and increased lipotoxicity in hepatocytes. Currently, there are limited treatment options for NASH due to lack of understanding of its molecular etiology. In the present study, we demonstrate that the expression of fat mass and obesity associated gene (FTO) is significantly increased in the livers of NASH patients and in a rodent model of NASH. Furthermore, using human hepatic cells, we show that genetic silencing of FTO protects against palmitate-induced oxidative stress, mitochondrial dysfunction, ER stress, and apoptosis in vitro. Taken together, our results show that FTO may have a deleterious role in hepatic cells during lipotoxic conditions, and strongly suggest that up-regulation of FTO may contribute to the increased liver damage in NASH.

Full Text

Duke Authors

Cited Authors

  • Lim, A; Zhou, J; Sinha, RA; Singh, BK; Ghosh, S; Lim, K-H; Chow, PK-H; Woon, ECY; Yen, PM

Published Date

  • October 21, 2016

Published In

Volume / Issue

  • 479 / 3

Start / End Page

  • 476 - 481

PubMed ID

  • 27651333

Pubmed Central ID

  • 27651333

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2016.09.086

Language

  • eng

Conference Location

  • United States