Diet-induced obesity induces oxidative stress and enhances H3K4me3 levels, driving nonresolving inflammation and myelopoiesis in hematopoietic stem and progenitor cells.

ABSTRACT: Diet-induced obesity leads to dysregulated myelopoiesis and nonresolving inflammation. Such dysregulation could involve epigenetic reprogramming, which can induce long-term changes in hematopoietic stem and progenitor cells (HSPCs). However, whether and how obesity-dysregulated HSPCs impact myelopoiesis in response to tissue injury are not fully understood. Here, we tested the hypothesis that obesity induces oxidative stress and histone H3 lysine-4 trimethylation (H3K4me3) in HSPCs, programming enhanced myelopoiesis and persistent inflammation, leading to impaired tissue recovery. Transfer of bone marrow HSPCs from high-fat diet-induced obese mice (HFD-HSPCs) to lean recipients was sufficient to drive nonresolving myelopoiesis and impaired tissue recovery from hindlimb ischemia. HFD-HSPCs

SUBMITTER: Takahashi K 

PROVIDER: S-EPMC12576131 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature