Nonalcoholic fatty liver disease stratification by liver lipidomics

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using highresolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.

Details

OriginalspracheEnglisch
Aufsatznummer100104
FachzeitschriftJournal of Lipid Research
Jahrgang62
PublikationsstatusVeröffentlicht - Nov. 2021
Peer-Review-StatusJa

Externe IDs

PubMed 34384788
ORCID /0000-0003-4375-3144/work/142255278
ORCID /0000-0003-2928-015X/work/145697700
Scopus 85117144822

Schlagworte

Schlagwörter

  • Biclustering analysis, Lipid biomarkers, Liver biopsies, Liver lipidome, NAFL;, NAFLD, NASH, Shotgun lipidomics, Sphingomyelins, Steatosis