Does iron overload in metabolic syndrome affect macrophage profile? A case control study

Autor: Bruno Pereira, Fabrice Lainé, Andrzej Mazur, Juliette Berger, Giulia Chinetti-Gbaguidi, Clément Lahaye, Marc Ruivard, Cécile Gladine
Přispěvatelé: CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], This study was funded by the University Hospital of Clermont-Ferrand (grant number Ruivard AOI 2013) and by the French Society of Internal Medicine (grant Marcel Simon 2014)., Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent
Jazyk: angličtina
Rok vydání: 2021
Předmět:
medicine.medical_specialty
Iron Overload
Iron
[SDV]Life Sciences [q-bio]
Macrophage polarization
Inflammation
Transferrin receptor
010501 environmental sciences
01 natural sciences
Biochemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Macrophage
Dysmetabolic iron overload syndrome
0105 earth and related environmental sciences
chemistry.chemical_classification
Ferritin
biology
business.industry
Macrophages
nutritional and metabolic diseases
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Phenotype
Metabolic syndrome
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
[SDV] Life Sciences [q-bio]
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition
Endocrinology
chemistry
Transferrin
Case-Control Studies
ABCA1
biology.protein
Molecular Medicine
Interleukin-4
medicine.symptom
business
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
030217 neurology & neurosurgery
Zdroj: Journal of Trace Elements in Medicine and Biology
Journal of Trace Elements in Medicine and Biology, Elsevier, 2021, 67, pp.126786. ⟨10.1016/j.jtemb.2021.126786⟩
Journal of Trace Elements in Medicine and Biology, 2021, 67, pp.126786. ⟨10.1016/j.jtemb.2021.126786⟩
ISSN: 0946-672X
1878-3252
DOI: 10.1016/j.jtemb.2021.126786⟩
Popis: International audience; AIMS: Dysmetabolic iron overload syndrome (DIOS) is common but the clinical relevance of iron overload is not understood. Macrophages are central cells in iron homeostasis and inflammation. We hypothesized that iron overload in DIOS could affect the phenotype of monocytes and impair macrophage gene expression. METHODS: This study compared 20 subjects with DIOS to 20 subjects with metabolic syndrome (MetS) without iron overload, and 20 healthy controls. Monocytes were phenotyped by Fluorescence-Activated Cell Sorting (FACS) and differentiated into anti-inflammatory M2 macrophages in the presence of IL-4. The expression of 38 genes related to inflammation, iron metabolism and M2 phenotype was assessed by real-time PCR. RESULTS: FACS showed no difference between monocytes across the three groups. The macrophagic response to IL-4-driven differentiation was altered in four of the five genes of M2 phenotype (MRC1, F13A1, ABCA1, TGM2 but not FABP4), in DIOS vs Mets and controls demonstrating an impaired M2 polarization. The expression profile of inflammatory genes was not different in DIOS vs MetS. Several genes of iron metabolism presented a higher expression in DIOS vs MetS: SCL11A2 (a free iron transporter, +76 %, p = 0.04), SOD1 (an antioxidant enzyme, +27 %, p = 0.02), and TFRC (the receptor 1 of transferrin, +59 %, p = 0.003). CONCLUSIONS: In DIOS, macrophage polarization toward the M2 alternative phenotype is impaired but not associated with a pro-inflammatory profile. The up regulation of transferrin receptor 1 (TFRC) in DIOS macrophages suggests an adaptive role that may limit iron toxicity in DIOS.
Databáze: OpenAIRE
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