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Investigation of the glycolytic switch induced by saturated fatty acid in human macrophages
Colonval, Megan; Fettweis, Grégory; L'homme, Laurent et al.
2017Keystone - Integrating metabolism and immunity joint with the meeting on cell death and inflammation
 

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Abstract :
[en] Obesity is a worldwide epidemic now recognized as a low-grade inflammatory disease, favoring the development of metabolic diseases and cancers. This systemic inflammation results from an accumulation of pro-inflammatory macrophages in adipose tissue. Recent work shows that these adipose tissue macrophages (ATMs) are characterized by M1/M2 and metabolic markers. Free fatty acids released in excess in obese adipose tissue could be proposed as triggers in shaping the ATM phenotype. Indeed, the treatment with saturated fatty acids (SFAs) recapitulates many features of the polarization seen in obese ATM. The goals of this research are to further characterize ATMs in obese patients and understand underlying transcriptional programs by using the model of human monocyte-derived macrophages (MDMs) treated with a common SFA. We performed the sequencing of the whole transcriptome of MDMs treated with saturated (C18:0) or unsaturated fatty acid (C18:1) complexed to BSA or with BSA alone. C18:0 treatment induces 3345 differentially expressed genes (q<0,05) while C18:1 treatment produces a weak response. As expected, gene set enrichment analysis (GSEA) demonstrates that C18:0 activates the transcription of genes involved in several M1 pathways. Interestingly, GSEA shows the enrichment of hypoxia and glycolysis gene sets, suggesting SFA-mediated aerobic glycolysis. We confirmed the glycolytic switch in C18 :0-treated MDMs by showing up-regulation of glycolysis enzymes and metabolites transporters and by measuring lactate production. We are currently investigating upstream events and have preliminary data suggesting SFAs do not induce this glycolytic switch through the TLR4 binding but has to be activated into acylCoA inside cells. This research project should lead to a better understanding of the metabolic reprogramming that occurs in ATMs during obesity and fuels an obesity-associated « sterile » inflammation.
Disciplines :
Endocrinology, metabolism & nutrition
Biochemistry, biophysics & molecular biology
Author, co-author :
Colonval, Megan ;  Université de Liège > GIGA-I3 > Immunometabolism and Nutrition
Fettweis, Grégory;  University of Liege > GIGA > Virology and Immunology
L'homme, Laurent;  University of Lille > Inserm- Pasteur Institute of Lille > U1011-EGID
Piette, Jacques ;  Université de Liège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Legrand, Sylvie ;  Université de Liège > GIGA-I3 > Virologie § Immunologie, Immunometabolism and Nutrition Group
Language :
English
Title :
Investigation of the glycolytic switch induced by saturated fatty acid in human macrophages
Publication date :
May 2017
Event name :
Keystone - Integrating metabolism and immunity joint with the meeting on cell death and inflammation
Event place :
Dublin, Ireland
Event date :
29th of May – 2nd of June 2017
Audience :
International
Available on ORBi :
since 27 June 2017

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