3 Key Takeaways
Plain English Summary- 01Core Finding
LCN2 + colonic macrophages persist after colitis resolution and retain heightened glycolysis together with durable histone H3K9 L-lactylation (H3K9la).
- 02Study Evidence
Tested in a standard-of-care clinical practice · clinical evidence review at the clinical practice stage.
- 03Practical Meaning
Benefits and risks vary by individual health history — discuss with a healthcare professional.
What This Means for You
Myeloid-specific Smarca4 deletion or pharmacological interruption of macrophage trafficking attenuates macrophage memory and protects against MASLD. Together, our findings define H3K9la-centered macrophage memory as a mobile pathogenic imprint that links prior colitis to increased susceptibility to metabolic liver disease.
The Discovery
Ulcerative colitis (UC) remission does not abolish susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanism linking prior intestinal inflammation to delayed liver injury remains unclear. We establish gut-liver axis memory transduction as an epigenetic-cellular-organ cascade in which inflammatory history is molecularly encoded and redeployed across organs. LCN2 + colonic macrophages persist after colitis resolution and retain heightened glycolysis together with durable histone H3K9 L-lactylation (H3K9la). These macrophages maintain a permissive memory state during remission and traffic to the liver, where they amplify steatosis under subsequent HFD challenge. Mechanistically, BRG1 cooperates with CEBPB at H3K9la-marked chromatin to sustain Lcn2 and Pkm transcription in a feed-forward circuit.
How It Works, Simply
This endocrinology research focuses on inflammation. Researchers evaluated it using a standard-of-care clinical practice · Clinical evidence review at the clinical practice stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
LCN2 + colonic macrophages persist after colitis resolution and retain heightened glycolysis together with durable histone H3K9 L-lactylation (H3K9la).
- 02Study Evidence
Tested in a standard-of-care clinical practice · clinical evidence review at the clinical practice stage.
- 03Practical Meaning
Benefits and risks vary by individual health history — discuss with a healthcare professional.
Biological Mechanism & Study Design
Study Design & Cohort
Clinical evidence review
Standard-of-care clinical practice · Clinical evidence review · Clinical Practice
Biological Pathway & Modality
Inflammation
Intervention: Histone lactylation scarring transmits metabolic and epigenetic memory across the
Experimental Findings & Endpoints
Ulcerative colitis (UC) remission does not abolish susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanism linking prior intestinal inflammation to delayed liver injury remains unclear.
We establish gut-liver axis memory transduction as an epigenetic-cellular-organ cascade in which inflammatory history is molecularly encoded and redeployed across organs. LCN2 + colonic macrophages persist after colitis resolution and retain heightened glycolysis together with durable histone H3K9 L-lactylation (H3K9la).
These macrophages maintain a permissive memory state during remission and traffic to the liver, where they amplify steatosis under subsequent HFD challenge. Mechanistically, BRG1 cooperates with CEBPB at H3K9la-marked chromatin to sustain Lcn2 and Pkm transcription in a feed-forward circuit.
Clinical Translation & Practice Context
Myeloid-specific Smarca4 deletion or pharmacological interruption of macrophage trafficking attenuates macrophage memory and protects against MASLD.
Together, our findings define H3K9la-centered macrophage memory as a mobile pathogenic imprint that links prior colitis to increased susceptibility to metabolic liver disease.
The Bottom Line · Clinical Pearl
“Together, our findings define H3K9la-centered macrophage memory as a mobile pathogenic imprint that links prior colitis to increased susceptibility to metabolic liver disease.”
Published in Cell Metabolism · Current Stage: Clinical Practice