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Strehlau, C. ; Broghammer, H. ; Gebhardt, C. ; Hoffmann, A. ; Hagemann, T. ; Midilli, S. ; Zimmer, R.S. ; Schubert, K.* ; Karagiannakou, V. ; Georgiadi, A. ; Ost, M.* ; Krüger, M.* ; Roth, L.* ; Krause, K.* ; Klöting-Blüher, N. ; Keller, M. ; Wabitsch, M.* ; Nuwayhid, R.* ; Stimson, R.H.* ; Stumvoll, M.* ; Blüher, M. ; Weiner, J. ; Heiker, J.T.

Adipocyte myoglobin is a determinant of energy expenditure and a potential target to limit obesity.

Adv. Sci.:e76191 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Thermogenesis ; Beta Oxidation ; Adipocyte ; Adipose Tissue ; Lipid Metabolism ; Myoglobin ; Fatty Acid ; Brown Adipose Tissue ; Downregulation And Upregulation ; Oxidative Phosphorylation; Brown-adipose-tissue; Cold-induced Thermogenesis; Diet-induced Thermogenesis; Fatty-acid; Mitochondria; Distinct; Muscle; Lipolysis; Cell; Identification
ISSN (print) / ISBN 2198-3844
e-ISSN 2198-3844
Zeitschrift Advanced science
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: e76191 Supplement: ,
Verlag Wiley
Verlagsort Weinheim
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Institute of Diabetes and Cancer (IDC)
Förderungen Federal Ministry of Research, Technology and Space
Germany's Excellence Strategy
Medical Research Council
Studienstiftung des Deutschen Volkes
Else Kroner-Fresenius Foundation
German Research Foundation