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Updated: May 29, 2025

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
LIMA1 O-GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing β-catenin-Regulated FASn Expression in
Fuji Yang1,2, Yifei Chen1,2, Guojun Zheng3
1Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Jiangsu University, Changzhou, 213017, China.
Abstract:
Hepatic lipid deposition is a key factor in progressing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigates the impact of the LIM domain and actin-binding protein 1 (LIMA1) on hepatic steatotic in MASLD and explore the underlying mechanisms. Increased levels of LIMA1 is observed in both serum and serum sEV of metabolic dysfunction-associated steatohepatitis (MASH) patients compared to healthy controls, with AUROC values of 0.76 and 0.86, respectively. Furthermore, increased LIMA1 O-GlcNAcylation is observed in mouse models of MASLD, and steatotic hepatocytes. Mechanistic studies revealed that steatosis upregulated Host cell factor 1 (HCF1) and O-GlcNAc transferase (OGT) expression, leading to catalyzed O-GlcNAcylation at the T662 site of LIMA1 and subsequent inhibition of its ubiquitin-dependent degradation. O-GlcNAcylation of LIMA1 enhances hepatocyte lipid deposition by activating β-catenin/FASn-associated signaling. Additionally, compared with their AAV8-TBG-LIMA1-WT counterparts, AAV8-TBG-LIMA1ΔT662 injection exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis in HFD-fed and CDAHFD-fed LIMA1 HKO (hepatocyte-specific knockout) mice. Moreover, LTH-sEV-mediated delivery of LIMA1 promoted MASLD progression by promoting hepatic stellate cell (HSC) activation. The findings suggest that serum sEV LIMA1 may be a potential noninvasive biomarker and therapeutic target for individuals with MASH.
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