| Autor: |
Dahik, Veronica D., KC, Pukar, Materne, Clément, Reydellet, Canelle, Lhomme, Marie, Cruciani-Guglielmacci, Céline, Denom, Jessica, Bun, Eric, Ponnaiah, Maharajah, Deknuydt, Florence, Frisdal, Eric, Hardy, Lise M., Durand, Hervé, Guillas, Isabelle, Lesnik, Philippe, Gudelj, Ivan, Lauc, Gordan, Guérin, Maryse, Kontush, Anatol, Soprani, Antoine |
| Zdroj: |
Science Translational Medicine; 12/11/2024, Vol. 16 Issue 777, p1-15, 15p |
| Abstrakt: |
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 ABCG1 expression and this inflammatory and metabolic status. Abolition of this protective, anti-inflammatory phenotype in Abcg1-deficient ATMs was achieved through restoration of lipoprotein lipase (Lpl) activity, thus delineating the importance of the Abcg1/Lpl axis in controlling ATM metabolic inflammation. Overall, our study identifies the rewiring of FA pools by Abcg1 as a major pathway orchestrating ATM plasticity and insulin resistance in DIO. Editor's summary: Lipid fluxes in adipose tissue can promote inflammation in obesity, but how this occurs is not clear. Dahik et al. show that the ATP-binding cassette G1 (ABCG1) on adipose tissue macrophages controls their inflammatory response to the abundant circulating saturated fatty acids present in obesity. Obese mice with myeloid-specific Abcg1 knockout showed reduced signs of inflammation, fatty acid metabolism, and lipid-associated macrophages, relationships also mirrored in human samples. The authors suggest that these results are attributable to a rerouting of saturated fatty acids from the membrane to lipid droplets, where they are neutralized. —Catherine Charneski [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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