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Factors such as genetics, lifestyle and environment also play a considerable role

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An accumulation of TCA intermediates may subsequently have an impact on the macrophage phenotype, e.g., by contributing to a pro-inflammatory phenotype [e.g., as shown for succinate (Tannahill et al., 2013) and oxaloacetate (Di Gioia et al., 2020)], fatty acid synthesis for membrane production or pro-inflammatory fatty acid-derivatives as prostaglandin [for citrate (Infantino et al., 2011)] or by triggering innate immune memory [for fumarate ( 4.2.1 TCA intermediate accumulation in M1 and trained macrophages More specifically, increased glutamine uptake in LPS-stimulated macrophages triggered the accumulation of succinate, which stabilized HIF1 and thereby increased the expression of the inflammatory mediator IL-1 (Tannahill et al., 2013)