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Article Dans Une Revue Metabolites Année : 2022

Mannose Receptor Deficiency Impacts Bone Marrow and Circulating Immune Cells during High Fat Diet Induced Obesity

Jasmine Nour
  • Fonction : Auteur
Annalisa Moregola
  • Fonction : Auteur
Monika Svecla
Lorenzo da Dalt
Rossella Bellini
Gian Paolo Fadini
  • Fonction : Auteur
Yoann Rombouts
Mattia Albiero
  • Fonction : Auteur
Fabrizia Bonacina
Giuseppe Danilo Norata

Résumé

The mannose receptor C-type 1 (Mrc1) is a C-type lectin receptor expressed on the immune cells and sinusoidal endothelial cells (ECs) of several tissues, including the bone marrow (BM). Parallel to systemic metabolic alterations and hematopoietic cell proliferation, high-fat diet (HFD) feeding increases the expression of Mrc1 in sinusoidal ECs, thus calling for the investigation of its role in bone marrow cell reprogramming and the metabolic profile during obesity. Mrc1 −/− mice and wild-type (WT) littermates were fed an HFD (45% Kcal/diet) for 20 weeks. Weight gain was monitored during the diet regimen and glucose and insulin tolerance were assessed. Extensive flow cytometry profiling, histological, and proteomic analyses were performed. After HFD feeding, Mrc1 −/− mice presented impaired medullary hematopoiesis with reduced myeloid progenitors and mature cells in parallel with an increase in BM adipocytes compared to controls. Accordingly, circulating levels of neutrophils and pro-inflammatory monocytes decreased in Mrc1 −/− mice together with reduced infiltration of macrophages in the visceral adipose tissue and the liver compared to controls. Liver histological profiling coupled with untargeted proteomic analysis revealed that Mrc1 −/− mice presented decreased liver steatosis and the downregulation of proteins belonging to pathways involved in liver dysfunction. This profile was reflected by improved glucose and insulin response and reduced weight gain during HFD feeding in Mrc1 −/− mice compared to controls. Our data show that during HFD feeding, mannose receptor deficiency impacts BM and circulating immune cell subsets, which is associated with reduced systemic inflammation and resistance to obesity development.
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hal-04240108 , version 1 (13-10-2023)

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Jasmine Nour, Annalisa Moregola, Monika Svecla, Lorenzo da Dalt, Rossella Bellini, et al.. Mannose Receptor Deficiency Impacts Bone Marrow and Circulating Immune Cells during High Fat Diet Induced Obesity. Metabolites, 2022, 12 (12), pp.1205. ⟨10.3390/metabo12121205⟩. ⟨hal-04240108⟩
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