Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from in vitro-induced steatotic hepatocytes

Thomas Kralj, Raju Khatri, Kenneth R. Brouwer, Kim L.R. Brouwer, Darren J. Creek

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid-enriched media. This study compared the lipidome of PHH cultured in fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acid-enriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid-enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients.

Original languageEnglish
Pages (from-to)1445-1452
Number of pages8
JournalFEBS Letters
Volume596
Issue number11
DOIs
Publication statusPublished - Jun 2022

Keywords

  • DILI
  • in vitro models
  • lipidomics
  • nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis
  • steatosis

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