2. Academic Validation
  3. Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions

Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions

  • EMBO Rep. 2024 Oct 18. doi: 10.1038/s44319-024-00278-4.
Najia Jeroundi # 1,  Charlotte Roy # 1,  Laetitia Basset 1,  Pascale Pignon 1,  Laurence Preisser 1,  Simon Blanchard 1 2,  Cinzia Bocca 3 4,  Cyril Abadie 5,  Julie Lalande 5,  Naïg Gueguen 3 4,  Guillaume Mabilleau 6 7,  Guy Lenaers 3 4,  Aurélie Moreau 8,  Marie-Christine Copin 1 7,  Guillaume Tcherkez 5 9,  Yves Delneste 1 2,  Dominique Couez 1,  Pascale Jeannin 10 11
Affiliations

Affiliations

  • 1 Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, LabEx IGO, F-49000, Angers, France.
  • 2 Immunology and Allergology laboratory, University Hospital, Angers, France.
  • 3 Univ Angers, Inserm, CNRS, MitoVasc, SFR ICAT, F-49000, Angers, France.
  • 4 Department of Genetics and Biochemistry, University Hospital, Angers, France.
  • 5 Univ Angers, INRAe, IRHS, SFR QUASAV, F-49000, Angers, France.
  • 6 Univ Angers, Nantes Université, Inserm, Oniris, RMeS, SFR ICAT, F-49000, Angers, France.
  • 7 Department of Cell and Tissue Pathology, University Hospital, Angers, France.
  • 8 Inserm, Nantes Université, University Hospital of Nantes, Centre de Recherche Translationnelle en Transplantation et Immunologie, Nantes, France.
  • 9 Research School of Biology, ANU College of Science, Australian National University, Canberra, ACT, 2601, Australia.
  • 10 Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, LabEx IGO, F-49000, Angers, France. pascale.jeannin@univ-angers.fr.
  • 11 Immunology and Allergology laboratory, University Hospital, Angers, France. pascale.jeannin@univ-angers.fr.
  • # Contributed equally.
PMID: 39424955 DOI: 10.1038/s44319-024-00278-4
Abstract

Macrophages fight Infection and ensure tissue repair, often operating at nutrient-poor wound sites. We investigated the ability of human macrophages to metabolize glycogen. We observed that the cytokines GM-CSF and M-CSF plus IL-4 induced glycogenesis and the accumulation of glycogen by monocyte-derived macrophages. Glyconeogenesis occurs in cells cultured in the presence of the inflammatory cytokines GM-CSF and IFNγ (M1 cells), via phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose-1,6-bisphosphatase 1 (FBP1). Enzyme inhibition with drugs or gene silencing techniques and 13C-tracing demonstrate that glutamine (metabolized by the TCA cycle), lactic acid, and glycerol were substrates of glyconeogenesis only in M1 cells. Tumor-associated macrophages (TAMs) also store glycogen and can perform glyconeogenesis. Finally, macrophage glycogenolysis and the pentose phosphate pathway (PPP) support cytokine secretion and phagocytosis regardless of the availability of extracellular glucose. Thus, glycogen metabolism supports the functions of human M1 and M2 cells, with inflammatory M1 cells displaying a possible dependence on glyconeogenesis.

Keywords

Cytokine secretion; Glycogenolysis; Glyconeogenesis; Macrophages; Phagocytosis.

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