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Global molecular landscape of early MASLD progression in human obesity

Zhao, Qing ; De Nardo, William ; Wang, Ruoyu LU ; Zhong, Yi ; Keles, Umur LU ; Sakalauskaite, Gabriele LU ; Zhao, Li Na LU ; Tay, Huiyi ; Youhanna, Sonia and Yan, Mengchao , et al. (2026) In eLife p.1-50
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fatty liver disease, MASLD, GTPases, fibrosis
in
eLife
pages
1 - 50
publisher
eLife Sciences Publications
ISSN
2050-084X
DOI
10.7554/eLife.109534.2.sa3
language
English
LU publication?
yes
id
523facf0-d45b-4a61-9794-b98b9e41a20a
date added to LUP
2026-02-26 12:04:05
date last changed
2026-02-26 13:09:37
@article{523facf0-d45b-4a61-9794-b98b9e41a20a,
  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.}},
  author       = {{Zhao, Qing and De Nardo, William and Wang, Ruoyu and Zhong, Yi and Keles, Umur and Sakalauskaite, Gabriele and Zhao, Li Na and Tay, Huiyi and Youhanna, Sonia and Yan, Mengchao and Xie, Ye and Kim, Youngrae and Lee, Sungdong and Lim, Rachel Liyu and Teo, Guoshou and Narayanaswamy, Pradeep and Burton, Paul R and Lauschke, Volker M and Choi, Hyungwon and Watt, Matthew J and Kaldis, Philipp}},
  issn         = {{2050-084X}},
  keywords     = {{fatty liver disease; MASLD; GTPases; fibrosis}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{1--50}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Global molecular landscape of early MASLD progression in human obesity}},
  url          = {{http://dx.doi.org/10.7554/eLife.109534.2.sa3}},
  doi          = {{10.7554/eLife.109534.2.sa3}},
  year         = {{2026}},
}