Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity
Source abstract
Abstract
ABSTRACT 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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Adipose Tissue and Metabolism · Hemoglobin structure and function · Adipokines, Inflammation, and Metabolic Diseases
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Helmholtz Institute for Metabolic Obesity and Vascular Research (HI‐MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig Leipzig Germany
Cell Biology Faculty 2 – Environment and Natural Science Brandenburg Technical University Cottbus‐Senftenberg Senftenberg Germany
Department of Molecular Systems Biology Helmholtz Centre for Environmental Research (UFZ) Leipzig Germany
Institute For Diabetes and Cancer Helmholtz Diabetes Center Helmholtz Munich Neuherberg Germany
German Center for Diabetes Research Neuherberg Germany
Paul Flechsig Institute – Centre of Neuropathology and Brain Research University of Leipzig Leipzig Germany
LeiCeM – Leipzig Center of Metabolism Leipzig University Leipzig Germany
Institute of Anatomy Faculty of Medicine Leipzig University Leipzig Germany
Department of Endocrinology Nephrology and Rheumatology Division of Endocrinology Leipzig University Medical Center Leipzig Germany
Department of Pediatrics and Adolescent Medicine Division of Pediatric Endocrinology and Diabetes Ulm University Medical Center Ulm Ulm Germany
Partner site Ulm German Center for Child and Adolescent Health (DZKJ) Ulm Germany
Department of Orthopaedic Trauma and Plastic Surgery Division of Plastic Aesthetic and Special Hand Surgery University Hospital Leipzig Leipzig Germany
Institute of Neuroscience and Cardiovascular Research University of Edinburgh Queen's Medical Research Institute Edinburgh UK
Partner site Leipzig German Center for Child and Adolescent Health (DZKJ) Leipzig Germany
Institute of Biochemistry Faculty of Life Sciences University of Leipzig Leipzig Germany
Funding
Deutsche Forschungsgemeinschaft · Medical Research Council · Studienstiftung des Deutschen Volkes
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