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 Kraft, David Tandio, Tong Shen, Kamil Borkowski, Oliver Fiehn, John W. Newman, Marianne Quiding‐Järbrink, Christina Biörserud, Peter Apelgren, Trude Staalesen, Carolina E. Hagberg, Jérémie Boucher, Ville Wallenius, Stephan Lange, Emma Börgeson
Abstract
, 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.