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. 2024 Dec 18;23(1):402.
doi: 10.1186/s12944-024-02380-x.

The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease

Clément J F Heymann  1 , Anne Linde Mak  2 , Adriaan G Holleboom  2 , Joanne Verheij  3 , Ronit Shiri-Sverdlov  4   5 , Saskia W C van Mil  6 , Maarten E Tushuizen  7 , Ger H Koek  5   8 , Aldo Grefhorst  9
Affiliations

The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease

Clément J F Heymann et al. Lipids Health Dis. .

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages.

Methods: We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring.

Results: Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH.

Conclusions: Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH.

Keywords: Lipidomics; Lipids; Lipoproteins; Liver; MASLD; Phospholipids/phosphatidylcholine.

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Conflict of interest statement

Declarations. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of the Amsterdam University Medical Centers (AUMC) and the Maastricht University Medical Center (MUMC+). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Relative abundance of plasma concentrations of the lipid classes in subjects with respect to their (A) hepatic steatosis grade, (B) fibrosis grade, and (C) NAS score. Data are shown as box plots. The inserted text mentions whether there is a significant difference (p < 0.05, Mann-Whitney U test) between the grades or scores for the specific lipid class
Fig. 2
Fig. 2
Heatmaps for the plasma concentrations for the 30 most affected individual lipids in subjects based on their (A) hepatic steatosis grade, (B) fibrosis grade, and (C) NAS score
Fig. 3
Fig. 3
Vulcanoplots of plasma lipids when comparing (A) individuals with MASLD without MASH to MASLD-free subjects, (B) individuals with MASLD who have MASH to MASLD_free subjects, and (C) individuals with MASLD with MASH to those without MASH. Red dots depict lipids of which the plasma concentration is significantly higher, green dots the lipids of which the plasma concentration is significantly lower. Figure C contains a zoom-in of the four statistically significant affected plasma lipids
Fig. 4
Fig. 4
Abundance of plasma PC(29:1) in subjects with respect to their (A) disease state, (B) hepatic steatosis grade, (C) fibrosis grade, and (D) NAS score. *, p < 0.05; **, p < 0.01; ***, p < 0.001 (Kruskal-Wallis test)
Fig. 5
Fig. 5
Abundance of plasma PC(36:2) in subjects with respect to their (A) disease state, (B) hepatic steatosis grade, (C) fibrosis grade, and (D) NAS score. *, p < 0.05; **, p < 0.01; ***, p < 0.001 (Kruskal-Wallis test)
Fig. 6
Fig. 6
Relative abundance of plasma triglycerides based on (A) the number of double bonds and (B) grouped for either having no double bonds, up to 3 double bonds or more than 3 double bonds. Data are shown as box plots
See this image and copyright information in PMC

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