The Warburg effect then and now: From cancer to inflammatory diseases

Abstract

Inflammatory immune cells, when activated, display much the same metabolic profile as a glycolytic tumor cell. This involves a shift in metabolism away from oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the Warburg effect. The result of this change in macrophages is to rapidly provide ATP and metabolic intermediates for the biosynthesis of immune and inflammatory proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates occurs notably in citrate for lipid biosynthesis, and succinate, which activates the transcription factor Hypoxia--inducible factor. In this review we take a look at the emerging evidence for a role for the Warburg effect in the immune and inflammatory responses. The reprogramming of metabolic pathways in macrophages, dendritic cells, and T cells could have relevance in the pathogenesis of inflammatory and metabolic diseases and might provide novel therapeutic strategies.

Doyne lecture 2016: intraocular health and the many faces of inflammation

“…113 Ageing, senescence, and bioenergetic sources O'Neill highlighted the prominence to the 'Warburg effect' in context to immune responses and the role in the pathogenesis of immune-mediated disorders, such as diabetes and atherosclerosis. [114][115][116] Extrapolating from Warburg's original observations that tumour cells undergo a bioenergetic switch (permissive for survival and proliferation), to aerobic glycolysis, we now appreciate that such bioenergetic switch occurs in the ageing and early AMD RPE. The Warburg effect rapidly provides ATP and enhances metabolic pathways to support immune cell function.…”

Mitochondrial carriers in inflammation induced by bacterial endotoxin and cytokines

“…macrophages, dendritic cells, neutrophils, and the adaptive system cells, B and T lymphocytes) are relatively inactive. Upon recognition of pathogens-associated molecular patterns these cells become activated and shift to a very active metabolic state to respond to high energy demand similar to that observed in tumour cells (Palsson-McDermott and O'Neill, 2013). Consequently, changes in the expression level of a large number of genes and an extensive metabolic reprogramming lead to acquisition of new functions, such as production of cytokines, intermediates for biosynthesis, lipid mediators, ROS and NO, as well as morphological changes, such as tissue remodelling, migration through tissues and cellular division (Pearce and Pearce, 2013).…”

Correlation Between Infection Status of Epstein-Barr Virus and 18F-Fluorodeoxyglucose Uptake in Patients with Advanced Gastric Cancer

“…This feature reflects the immunogenicity of EBV, and this immune response by the host could be one reason for a better prognosis (18). The fact that increased 18 F-FDG uptake has been observed in metabolically-active inflammatory cells (27) could be one explanation for the relationship of 18 F-FDG uptake in EBVaGC. A recent study presented the association between metabolic parameters on 18 F-FDG-PET and intra-tumor expression of immune-related markers in patients with nonsmall cell lung cancer (28).…”