Research
Hormonal
Accumulation of succinate and itaconate in classically activated macrophages stabilizes HIF-1alpha, which promotes further glycolysis and inflammation, creating a feedback loop.
Specific metabolites (succinate) can act as signaling molecules to lock immune cells into an inflammatory state by stabilizing key transcription factors.
GoodSupportsHIGH confidence
Higher levels of succinate also lead to stabilization of transcription factor hypoxia-inducible factor 1-alpha (HIF-1a) because succinate inhibits prolyl hydroxylase domain proteins... The stabilization of HIF-1a will lead to its binding to hypoxia response elements on target genes and induce their expression. HIF-1a in fact promotes the switch to glycolysis by inducing expression of glycolytic enzymes...
Why this rating
Reviewed mechanism with strong supporting literature cited.
Source
Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites
Sara Russo et al. · Frontiers in Immunology · 2021
DOI 10.3389/fimmu.2021.746151
narrative_reviewCited 246×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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- In obesity and type 2 diabetes, adipose tissue macrophages undergo 'metabolic activation' characterized by high glycolysis and lipid internalization, which drives insulin resistance and chronic inflammation without exhibiting the classical M1 activation markers.Good
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