iScience (Jul 2022)
Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures
- Matúš Soták,
- Meenu Rohini Rajan,
- Madison Clark,
- Matthew Harms,
- Alankrita Rani,
- Jamie D. Kraft,
- David Tandio,
- Tong Shen,
- Kamil Borkowski,
- Oliver Fiehn,
- John W. Newman,
- Marianne Quiding-Järbrink,
- Christina Biörserud,
- Peter Apelgren,
- Trude Staalesen,
- Carolina E. Hagberg,
- Jeremie Boucher,
- Ville Wallenius,
- Stephan Lange,
- Emma Börgeson
Affiliations
- Matúš Soták
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 41345 Gothenburg, Sweden
- Meenu Rohini Rajan
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 41345 Gothenburg, Sweden
- Madison Clark
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden
- Matthew Harms
- Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Alankrita Rani
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 41345 Gothenburg, Sweden
- Jamie D. Kraft
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden
- David Tandio
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden
- Tong Shen
- NIH West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA
- Kamil Borkowski
- NIH West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA
- Oliver Fiehn
- NIH West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA
- John W. Newman
- NIH West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA; Department of Nutrition, University of California Davis, Davis, CA 95616, USA; USDA, ARS, Western Human Nutrition Research Center, Davis, USA
- Marianne Quiding-Järbrink
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
- Christina Biörserud
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Peter Apelgren
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Plastic Surgery, Gothenburg, Sweden
- Trude Staalesen
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Plastic Surgery, Gothenburg, Sweden
- Carolina E. Hagberg
- Division of Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- Jeremie Boucher
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden; The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Ville Wallenius
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Stephan Lange
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Division of Cardiology, School of Medicine, University of California San Diego, San Diego, CA, USA
- Emma Börgeson
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden; Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 41345 Gothenburg, Sweden; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 7
p. 104602
Abstract
Summary: Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects against obesity-induced systemic disease in mice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularly well to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generating enzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
