Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity
Nutritional overflow and a positive energy balance are hallmarks of metabolic diseases including obesity and type 2 diabetes. Brown and beige adipocytes maintain systemic metabolic homeostasis by clearing and oxidizing energy-rich nutrients during thermogenic activation. Myoglobin (MB) is classically regarded as a muscle-associated oxygen-binding protein; however it is also expressed in brown and beige adipocytes, where it contributes to intracellular lipid handling and oxidative metabolism. Here, we report that loss of MB exclusively in adipose tissue (AT) lowers whole-body energy expenditure, impairs thermoregulation, and increases susceptibility to diet-induced obesity. AT-specific MB knockout (ATMBKO) mice exhibit elevated circulating triglycerides (TG) and fatty acids, indicating defective lipid clearance and utilization. Omics analyses reveal coordinated downregulation of oxidative phosphorylation, fatty acid metabolism, and myogenic programs. Conversely, restoration of MB in MB knockout (MBKO) mice improves metabolism in vivo. MB expression determines the capacity for mitochondrial fatty acid oxidation in brown adipocytes, whereas MB overexpression in primary human white adipocytes enhances thermogenic activity, confirming functional relevance of MB in human AT. Together, these findings establish MB as a key determinant of thermogenic lipid metabolism and energy expenditure in vivo and increasing adipocyte MB expression could increase energy expenditure and complement obesity treatment strategies.
Authors
- Maria Keller (ORCID: https://orcid.org/0000-0003-4026-8530)
- Christian Strehlau
- Kerstin Krause (ORCID: https://orcid.org/0000-0003-1766-3698)
- Roland H. Stimson (ORCID: https://orcid.org/0000-0002-9002-6188)
- Helen Broghammer
- M Stumvoll
- Mario Ost (ORCID: https://orcid.org/0000-0002-1811-2049)
- Anastasia Georgiadi (ORCID: https://orcid.org/0000-0002-9648-8682)
- Kristin Schubert (ORCID: https://orcid.org/0000-0003-4365-084X)
- Juliane Weiner (ORCID: https://orcid.org/0000-0003-1055-6005)
- Nora Klöting (ORCID: https://orcid.org/0000-0002-7625-7254)
- Claudia Gebhardt
- John T. Heiker (ORCID: https://orcid.org/0000-0003-2822-3006)
- Martin Wabitsch (ORCID: https://orcid.org/0000-0001-6795-8430)
- Martin Krüger
- Vasiliki Karagiannakou
- A Hoffmann
- Tobias Hagemann
- Rima Nuwayhid
- Şeyma Midilli
- Rachel S. Zimmer (ORCID: https://orcid.org/0009-0001-5462-7007)
- Lisa Roth
- Matthias Blüher
Institutions
- Helmholtz Centre for Environmental Research (DE)
- Leipzig University of Applied Sciences (DE)
- Universität Ulm (DE)
- Helmholtz Zentrum München (DE)
- Leipzig Heart Institute (DE)
- University Hospital Leipzig (DE)
- German Centre for Cardiovascular Research (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- University Hospital Ulm (DE)
- German Center for Diabetes Research (DE)
- The Queen's Medical Research Institute (GB)
- Heinrich Heine University Düsseldorf (DE)
- Brandenburg University of Technology Cottbus-Senftenberg (DE)
- Leipzig University (DE)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1002/advs.76191
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Studienstiftung des Deutschen Volkes
- Medical Research Council