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ResearchIn-Press PreviewHepatologyImmunologyMetabolism Open Access | 10.1172/jci.insight.200231

Interleukin-10 attenuates metabolic dysfunction-associated steatotic liver disease via modulation of hepatic responses to lipotoxicity

Akira Kado,1 Kazuya Okushin,1 Takeya Tsutsumi,2 Toshiyuki Kishida,3 Kazuhiko Ikeuchi,3 Hiroshi Yotsuyanagi,4 Kyoji Moriya,2 Kazuhiko Koike,1 and Mitsuhiro Fujishiro1

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Kado, A. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Okushin, K. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Tsutsumi, T. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Kishida, T. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Ikeuchi, K. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Yotsuyanagi, H. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Moriya, K. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Koike, K. in: PubMed | Google Scholar

1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

3Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Find articles by Fujishiro, M. in: PubMed | Google Scholar |

Published April 23, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.200231.
Copyright © 2026, Kado et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 23, 2026 - Version history
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Abstract

Lipotoxicity associated with metabolic dysfunction-associated steatotic liver disease (MASLD) causes dysregulated fatty acid (FA) and glucose metabolism, inducing cellular energy imbalance, oxidative stress (OS), and hepatocellular injury. Interleukin (IL)-10 is altered in MASLD, including increased IL-10 transcripts in peripheral immune cells; however, its role in hepatic responses to lipotoxic stress remains unclear. We evaluated whether IL-10 treatment attenuates lipotoxic injury and MASLD-related phenotypes in vivo and in vitro to reveal MASLD treatment strategies. As MASLD models, in vivo high-fat diet mice and in vitro normal human hepatocytes under palmitic acid exposure, with confirmatory experiments in HepG2 cells, were used and treated with IL-10. We assessed FA and glucose metabolism, OS, and apoptosis with histological changes and mechanisms related to hepatocellular viability/metabolic activity and stress-responsive survival signaling in vitro. IL-10 modulated FA synthesis and β-oxidation, reducing lipid accumulation, and altered glucose metabolic pathways, consistent with improved glucose handling under lipotoxic stress. Furthermore, IL-10 reduced OS and cell death markers while enhancing antioxidant responses, consistent with hepatocellular protection. These data suggest that IL-10 attenuates lipotoxic injury by modulating hepatic response pathways, thereby improving MASLD-related phenotypes, and supports the potential of IL-10 as a therapeutic target for MASLD.

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