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Updated: Sep 9, 2026
In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
Published on: July 19, 2024
Lipocalin 13 Mitigates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Inhibiting the ADRB2/ERK
Xingliang Qin1, Yu Hong2,3, Weishu Ren2
1Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormalities in secreted protein biosynthesis. A comprehensive understanding of secreted proteins could lead to improved diagnostics and therapies for MASLD. This study investigates the therapeutic potential of lipocalin 13 (LCN13), a lipocain family protein, in MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH).
Methods:
We screened critical lipocalins linked to MASLD using the Gene Expression Omnibus databases, analysing data from both mice and humans. The functional role of LCN13 was assessed in global knockout mice and in two murine MASLD models. We investigated LCN13's impact on glucose intolerance, insulin resistance, hepatic steatosis, and metabolic dysfunction in C57BL/6J mice subjected to high-fat and methionine-choline-deficient diets. The methodologies employed included Western blotting, quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), haematoxylin and eosin staining (H&E), and Oil Red O staining. Furthermore, we employed co-immunoprecipitation (co-IP), LC-MS/MS, Western blotting, and qPCR to investigate the underlying mechanisms involved.
Results:
LCN13 expression was significantly reduced in both mouse and human MASLD cases. Administration of recombinant LCN13 protein (rLCN13) improved conditions like hepatic steatosis, inflammation, and hepatocyte injury in diet-challenged mice, whereas LCN13 knockout worsened these effects. Mechanistically, LCN13 was found to inhibit the activation of the ERK signalling pathway by interacting with the extracellular loop 2 (ECL2) of the ADRB2, thereby representing a novel target for LCN13. This interaction suppressed CD36 expression, impacting lipid transport signalling and subsequently slowing the MASLD and MASH progression.
Conclusions:
Our findings highlight the protective role of LCN13 in MASLD and MASH, offering a new therapeutic approach for these metabolic disorders.
