A20 deficiency in myeloid cells protects mice from diet-induced obesity and insulin resistance due to increased fatty acid metabolism

Leen Catrysse, Bastiaan Maes, Parul Mehrotra, Arne Martens, Esther Hoste, Liesbet Martens, Christian Maueröder, Anneleen Remmerie, Anna Bujko, Karolina Slowicka, Mozes Sze, Hanna Vikkula, Bart Ghesquière, Charlotte L. Scott, Yvan Saeys, Bart van de Sluis, Kodi Ravichandran, Sophie Janssens, Geert van Loo

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity-induced inflammation is a major driving force in the development of insulin resistance, type 2 diabetes (T2D), and related metabolic disorders. During obesity, macrophages accumulate in the visceral adipose tissue, creating a low-grade inflammatory environment. Nuclear factor κB (NF-κB) signaling is a central coordinator of inflammatory responses and is tightly regulated by the anti-inflammatory protein A20. Here, we find that myeloid-specific A20-deficient mice are protected from diet-induced obesity and insulin resistance despite an inflammatory environment in their metabolic tissues. Macrophages lacking A20 show impaired mitochondrial respiratory function and metabolize more palmitate both in vitro and in vivo. We hypothesize that A20-deficient macrophages rely more on palmitate oxidation and metabolize the fat present in the diet, resulting in a lean phenotype and protection from metabolic disease. These findings reveal a role for A20 in regulating macrophage immunometabolism.

Original languageEnglish
Article number109748
JournalCell Reports
Volume36
Issue number12
DOIs
StatePublished - Sep 21 2021

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