Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep;75(3):524-535.
doi: 10.1016/j.jhep.2021.04.013. Epub 2021 Apr 20.

Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis

Geraldine J Ooi  1 , Peter J Meikle  2 , Kevin Huynh  2 , Arul Earnest  3 , Stuart K Roberts  4 , William Kemp  4 , Benjamin L Parker  5 , Wendy Brown  6 , Paul Burton  6 , Matthew J Watt  7
Affiliations

Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis

Geraldine J Ooi et al. J Hepatol. 2021 Sep.

Abstract

Backgrounds & aims: Obesity often leads to non-alcoholic fatty liver disease (NAFLD), which can progress from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH). The accumulation of certain lipid subtypes is linked with worsening metabolic and liver disease, however, specific changes during progression from No-NAFL to NAFL then NASH are unresolved. Herein, we characterise the liver, adipose tissue and plasma lipidome of worsening NAFLD in obesity, and evaluate the utility of plasma lipids as biomarkers of NAFLD.

Methods: Venous blood, liver, visceral and subcutaneous adipose tissue samples were obtained from 181 patients undergoing bariatric surgery. NAFLD severity was assessed histologically. Lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry.

Results: The liver lipidome showed substantial changes with increasing steatosis, with increased triacylglycerols, diacylglycerols and sphingolipids including ceramide, dihydroceramide, hexosyl-ceramide and GM3 ganglioside species. These lipid species were also increased in plasma with increasing hepatic steatosis and showed strong correlations with liver lipids. Adipose tissue lipidomes showed no correlation with NAFLD. There were no significant changes in liver lipids with NASH compared to NAFL. The addition of plasma lipid variables to routine markers yielded significant improvements in diagnostic accuracy for NASH (AUROC 0.667 vs. 0.785, p = 0.025).

Conclusion: Overall, these data provide a detailed description of the lipidomic changes with worsening NAFLD, showing significant changes with steatosis but no additional changes with NASH. Alterations in the liver lipidome are paralleled by similar changes in plasma. Further investigation is warranted into the potential utility of plasma lipids as non-invasive biomarkers of NAFLD in obesity.

Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterised by distinct changes in the liver lipidome with steatosis. The development of non-alcoholic steatohepatitis (NASH) does not result in further changes in the lipidome. Lipids within body fat do not appear to influence the lipid profile of the liver or blood. Changes in liver lipids are paralleled by changes in blood lipids. This has potential to be developed into a non-invasive biomarker for NAFLD.

Clinical trial number: ACTRN12615000875505.

Keywords: adipose tissue; ceramides; lipid metabolism; lipid species; lipidomics; nonalcoholic fatty liver disease; obesity; triglycerides.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest WB reports financial support for a bariatric surgery registry from the Commonwealth of Australia, Apollo Endosurgery, Covidien, Johnson and Johnson, Gore and Applied Medical. She has also received a speaker’s honorarium from Merck Sharpe and Dohme and a speaker’s honorarium and fees from participation in a scientific advisory board from Novo Nordisk. The Bariatric Registry and the honorariums are outside of the submitted work. GJO was supported by scholarships from the National Health and Medical Research Council (NHMRC) (APP1114811) and the Royal Australasian College of Surgeons. MJW is supported by a Senior Research Fellowship from the NHMRC (APP1077703) and has received financial support from Gilead Sciences. PJM, BLP, KH, AE, SKR, and WK have no disclosures or conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details.

Publication types

LinkOut - more resources