Authors: Veronica D. Dahik, Pukar KC, Clément Materne, Canelle Reydellet, Marie Lhomme, Céline Cruciani-Guglielmacci, Jessica Denom, Eric Bun, Maharajah Ponnaiah, Florence Deknuydt, Eric Frisdal, Lise M. Hardy, Hervé Durand, Isabelle Guillas, Philippe Lesnik, Ivan Gudelj, Gordan Lauc, Maryse Guérin, Anatol Kontush, Antoine Soprani, Christophe Magnan, Marc Diedisheim, Olivier Bluteau, Nicolas Venteclef, Wilfried Le Goff
Published: 2024-12-11
DOI: 10.1126/scitranslmed.adi6682
Source: Full article
The mechanisms governing adipose tissue macrophage (ATM) metabolic adaptation during diet-induced obesity (DIO) are poorly understood. In obese adipose tissue, ATMs are exposed to lipid fluxes, which can influence the activation of specific inflammatory and metabolic programs and contribute to the development of obesity-associated insulin resistance and other metabolic disorders. In the present study, we demonstrate that the membrane ATP-binding cassette g1 (Abcg1) transporter controls the ATM functional response to fatty acids (FAs) carried by triglyceride-rich lipoproteins, which are abundant in high-energy diets. Mice genetically lacking Abcg1 in the myeloid lineage presented an ameliorated inflammatory status in adipose tissue and reduced insulin resistance. Abcg1-deficient ATMs exhibited a less inflammatory phenotype accompanied by a low bioenergetic profile and modified FA metabolism. A closer look at the ATM lipidome revealed a shift in the handling of FA pools, including a redirection of saturated FAs from membrane phospholipids to lipid droplets, leading to a reduction in membrane rigidity and neutralization of proinflammatory FAs. ATMs from human individuals with obesity presented the same reciprocal relationship between