Global molecular landscape of early MASLD progression in obesity

Year: 2025

Type: preprint

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is often asymptomatic early on but can progress to irreversible conditions like cirrhosis. Due to limited access to human liver biopsies, systematic and integrative molecular resources remain scarce. In this study, we performed transcriptomic analyses on liver and metabolomic analyses on liver and plasma samples from morbidly obese individuals without liver pathology or at early-stage MASLD. While, the plasma metabolomic profile did not fully mirror liver histological features, dual-omics integration of liver samples revealed significantly remodeled lipid and amino acid metabolism pathways. Integrative network analysis uncoupled metabolic remodeling and gene expression as independent features of hepatic steatosis and fibrosis progression, respectively. Notably, GTPases and their regulators emerged as a novel class of genes linked to early liver fibrosis. This study offers a detailed molecular landscape of early MASLD in obesity and highlights potential targets of obesity-linked liver fibrosis.

Source: eLife

DOI: 10.7554/elife.109534.1

Institutions: National University of Singapore, Life Sciences Institute, The University of Melbourne, Lund University, First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Karolinska Institutet, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Sciex (Canada), The Alfred Hospital, Monash University

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funder: Vetenskapsrådet

Award: Metabolic signaling from the liver in type 2 diabetes

OpenAlex ID: W4417331594