Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures

iScience

Jamie D. Kraft¹  Marianne Quiding-Järbrink¹  Madison Clark¹  Peter Apelgren²  Meenu Rohini Rajan²  Alankrita Rani²  John W. Newman²  Tong Shen²  Carolina E. Hagberg²  Kamil Borkowski³  Oliver Fiehn⁴  Matthew Harms⁴  David Tandio⁴  Matúš Soták⁴  Trude Staalesen⁴  Christina Biörserud⁴  Stephan Lange⁵  Jeremie Boucher⁵  Ville Wallenius⁵  Emma Börgeson⁵ 

[1] Region Vaestra Goetaland, Sahlgrenska University Hospital, Department of Clinical Physiology, 41345 Gothenburg, Sweden;Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden;Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden;Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden;NIH West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA;

关键词: Precision medicine;    Biological sciences;    Physiology;    Human metabolism;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown