Journal article
Myeloid HDAC7 drives liver inflammation and systemic glucose dysregulation during diet‐induced obesity
Clinical & Translational Immunology, Vol.15(6), pp.1-20
2026
Abstract
Objectives
Histone deacetylase 7 (HDAC7), a classical HDAC family member, promotes LPS-inducible glycolysis and inflammatory mediator production in macrophages, innate immune cells that contribute to pathology in metabolic diseases. Here, we investigated myeloid HDAC7 functions in obesity-driven metabolic disease.
Methods
We used gain- and loss-of-function genetic approaches in mice to investigate myeloid HDAC7 functions in hepatic inflammation and metabolic disease, as well as associations with hepatic gene signatures characteristic of advanced chronic liver disease (CLD).
Results
Transgenic expression of Hdac7 in myeloid cells increased liver inflammation and liver mRNA levels of Ccl2 and Il1b, key inflammatory mediators linked to CLD. Liver glycogen levels were also decreased, another feature of CLD. Transgenic expression of Hdac7 in myeloid cells mimicked the hepatic inflammatory phenotype that was observed in mice fed a high fat, high cholesterol and high sucrose (HFHCHS) diet, an obesity model that mimics some features of metabolic dysfunction-associated steatotic liver disease. In myeloid Hdac7 transgenic mice fed a HFHCHS diet, relative weight gain was increased, fasted glucose levels were elevated, and glucose tolerance was dysregulated by comparison to control mice. Conversely, fasted blood glucose levels were reduced and glucose tolerance was improved in myeloid Hdac7-deleted mice on a HFHCHS diet. HDAC7 mRNA levels were also elevated in the livers of people with advanced CLD and spatial transcriptomics revealed that myeloid HDAC7 directs hepatic gene signatures characteristic of advanced CLD.
Conclusion
Myeloid HDAC7 contributes to hepatic inflammation and systemic glucose dysregulation in a mouse model of obesity and liver inflammation.
Details
- Title
- Myeloid HDAC7 drives liver inflammation and systemic glucose dysregulation during diet‐induced obesity
- Authors
- Yizhuo Wang - The University of QueenslandDivya Ramnath - The University of QueenslandKaustav Das Gupta - The University of QueenslandP Prakrithi - The University of QueenslandKavita Bisht - Translational Research InstituteGregory C Miller - The University of QueenslandZherui Xiong - The University of QueenslandYujun Wan - The University of QueenslandEllen N Tejo - Translational Research InstituteJames EB Curson - The University of QueenslandRishika Abrol - The University of QueenslandSahar Keshvari - Translational Research InstituteKimberley S Gunther - The University of QueenslandJordan D Atkinson - The University of QueenslandZhixuan Loh - The University of QueenslandJessica A Engel - QIMR Berghofer Medical Research InstituteChristian R Engwerda - QIMR Berghofer Medical Research InstituteSabrina Sofia Burgener - The University of QueenslandKate Schroder - The University of QueenslandDavid P Fairlie - The University of QueenslandAndrew D Clouston - The University of QueenslandElizabeth E Powell - The University of QueenslandKatharine M Irvine - Translational Research InstituteMitchell A Sullivan - University of the Sunshine CoastJean‐Pierre Lévesque - Translational Research InstituteQuan Nguyen - The University of QueenslandMatthew J Sweet (Corresponding Author) - The University of QueenslandDenuja Karunakaran (Corresponding Author) - The University of Queensland
- Publication details
- Clinical & Translational Immunology, Vol.15(6), pp.1-20
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2026
- DOI
- 10.1002/cti2.70100
- ISSN
- 2050-0068
- Copyright note
- © 2026 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Data Availability
- The data that support the findings of this study are available from the corresponding author upon reasonable request.
- Grants
- Grant note
- Novartis Foundation for Medical-Biological Research Fellowship. Grant Number: 21C133 / Swiss National Science Foundation Postdoc Mobility Fellowship. Grant Number: P2BEP3_191800 / Australian Infectious Disease Research Centre seed grant.
- Organisation Unit
- School of Health - Biomedicine; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991233182402621
- Output Type
- Journal article
Metrics
1 Record Views