Lipid Metabolites Emerge as Noninvasive Diagnostic Tool in MASH

A lipidomic analysis identified higher concentrations of deoxycholic acid, triacylglycerols (TAG), ceramides, and certain phospholipids in patients with metabolic dysfunction–associated steatohepatitis (MASH). These insights, published in PLoS One, demonstrated how a lipid metabolite panel could serve as a noninvasive and valuable diagnostic tool in this patient population.1

Lipid metabolite assays could be a potential noninvasive diagnostic alternative for patients with MASH who otherwise may need a liver biopsy | image credit: Vlad - stock.adobe.com

Previously, the authors conducted an untargeted metabolomic analysis that evaluated the serum samples of patients with hepatatic histological diagnoses. Their results identified distinguishable lipid metabolites involved in metabolic dysfunction–associated steatotic liver disease (MASLD) and MASH, adding to an emerging body of lipidomic and metabolomic literature that associates certain metabolites with the MASLD/MASH pathway.2 The current study aims to shed further light on MASH’s lipid metabolite profile through an untargeted lipidomic assay that uses liquid chromatography alongside mass spectrometry (LC/MS). These efforts, they add, remain an important venture as researchers have sought out noninvasive biomarkers for MASH diagnosis to offer alternatives to often less-desirable liver biopsies.3

Serum samples collected from 216 women with morbid obesity (MO; body mass index ≥ 40 kg/m2) for the untargeted lipidomic analysis with LC/MS,1 which reflected the patient cohort from their previous study. In total, 44 women were grouped in a normal liver (NL) category whereas the remaining 172 were grouped in the MASLD category. Throughout the MASLD group, 66 women were characterized as having simple steatosis (SS) and 106 as having MASH grades I-II.

There were no significant differences observed in patients’ cholesterol, high-density lipoprotein, or low-density lipoprotein levels. Patients with MASH and SS exhibited significantly greater glucose levels, insulin, hemoglobin A1c, gamma-glutamyl transferase, alanine transaminase, aspartate transaminase, and TAG compared with the patients with NL. The authors added, however, that the MASH and SS groups did not present with significant variations.

The analysis did not reveal any decreased concentrations of lipid metabolites for those in the MASLD group; rather, these patients exhibited higher levels of TAG, ceramides, phosphatidylethanolamines (PE), phosphatidylcholines (PC), and phosphatidylinositols (PI) compared with those in the NL group. Subgroup analyses revealed that those with SS had greater levels of TAG, PI, PE, PC, diacylglycerols, and ceramides compared with NL individuals; those with MASH had greater levels of PE, PC, TAG, deoxycholic acid, ceramides, PI, and lyso-PI (LPI). Comparing the MASH and SS groups, higher levels of LPI, PC, PE and fatty acid 9-hydroxy-octadecadenoic acid were seen in patients with MASH.

Although no significant differences were found between NL and MASLD, the authors noted how 10 lipid metabolites were seen that differentiated MASH from NL, 11 that differentiated SS from NL, and 6 that differentiated MASH from SS.

The authors felt these results may have limited generalizability because they only evaluated fertile women with MO; however, they noted the importance of a homogenous cohort in their evaluation. Additionally, they mentioned a lack of exclusive lipid metabolite profiles to uniquely distinguish SS and MASH, as well as the potential for environmental factors (such as temperature, pressure, etc) to influence variability in their LC/MS technique.

“This study underscores the importance of lipidomics in understanding MASLD progression and reinforces the need for targeted omics analyses to validate these findings and improve diagnostic accuracy,” the authors concluded.

References

1. Bertran L, Capellades J, Abelló S, Richart C. Untargeted lipidomic analysis of metabolic dysfunction-associated steatohepatitis in women with morbid obesity. PLoS One. 2025;20(3):e0318557. doi:10.1371/journal.pone.0318557

2. Bertran L, Capellades J, Abelló S, et al. LC/MS-based untargeted metabolomics study in women with nonalcoholic steatohepatitis associated with morbid obesity. Int J Mol Sci. 2023;24(12):9789. doi:10.3390/ijms24129789

3. Kouvari M, Valenzuela-Vallejo L, Guatibonza-Garcia V, et al. Liver biopsy-based validation, confirmation and comparison of the diagnostic performance of established and novel non-invasive steatotic liver disease indexes: results from a large multi-center study. Metabolism. 2023;147:155666. doi:10.1016/j.metabol.2023.155666