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

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-10-18 DOI:10.1038/s44319-024-00278-4

Najia Jeroundi, Charlotte Roy, Laetitia Basset, Pascale Pignon, Laurence Preisser, Simon Blanchard, Cinzia Bocca, Cyril Abadie, Julie Lalande, Naïg Gueguen, Guillaume Mabilleau, Guy Lenaers, Aurélie Moreau, Marie-Christine Copin, Guillaume Tcherkez, Yves Delneste, Dominique Couez, Pascale Jeannin

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引用次数: 0

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.

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谷氨酰胺、乳酸和甘油的糖生成和糖醛酸生成支持人体巨噬细胞的功能。

巨噬细胞能抗感染并确保组织修复，但通常在缺乏营养的伤口部位工作。我们研究了人类巨噬细胞代谢糖原的能力。我们观察到，细胞因子 GM-CSF 和 M-CSF 加 IL-4 可诱导单核巨噬细胞糖原生成和糖原累积。在有炎症细胞因子 GM-CSF 和 IFNγ（M1 细胞）存在的情况下培养的细胞会通过磷酸烯醇丙酮酸羧激酶 2（PCK2）和果糖-1,6-二磷酸酶 1（FBP1）发生糖原生成。通过药物或基因沉默技术抑制酶的活性，以及 13C 追踪技术证明，只有在 M1 细胞中，谷氨酰胺（通过 TCA 循环代谢）、乳酸和甘油才是糖元生成的底物。肿瘤相关巨噬细胞（TAMs）也储存糖原，并能进行糖元生成。最后，无论细胞外葡萄糖是否存在，巨噬细胞糖原分解和磷酸戊糖途径（PPP）都支持细胞因子分泌和吞噬作用。因此，糖原代谢支持人类 M1 和 M2 细胞的功能，炎症性 M1 细胞可能依赖于糖原生成。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.