Obesity Disrupts H3K4me3-Mediated Lactate Accumulation and Efferocytosis in Hypoxic Macrophages - PubMed

4 hours ago

Obesity impairs macrophage adaptation to hypoxia by disrupting H3K4me3-mediated epigenetic changes.
In obese mice, macrophages show decreased H3K4me3, reduced lactate accumulation, and lower histone lactylation under hypoxia.
Impaired lactate levels in obesity lead to decreased efferocytosis capacity in hypoxic macrophages, reversible with glucose or lactate supplementation.
Bone marrow transplantation reveals that maladapted hypoxia response is imprinted in macrophage precursors in obese mice.
Disruption of H3K4me3 demethylase KDM5A enhances hypoxia-induced H3K4me3, lactate accumulation, and gene expression in macrophages.
In obese mice, delayed wound healing is associated with low extracellular lactate levels post-wounding compared to normal mice.
Findings link obesity to disrupted metabolic adaptation via H3K4me3 and lactate, affecting macrophage efferocytosis and healing in hypoxic conditions.

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