Histone lactylation scarring transmits metabolic and epigenetic memory across the gut-liver axis.

Histone lactylation in colonic macrophages creates a mobile epigenetic memory that promotes liver steatosis after colitis, linking gut inflammation to metabolic liver disease.

• Why it matters: Understanding how intestinal inflammation influences subsequent liver pathology is crucial for preventing MASLD in patients with a history of ulcerative colitis, addressing a significant clinical gap.
• What they did: The study examined macrophages from mice with colitis, revealing persistent H3K9la histone modifications and heightened glycolysis that enable these cells to traffic to the liver and exacerbate steatosis under a high-fat diet, using genetic and pharmacological interventions.
• The result: Disrupting macrophage memory or trafficking reduces liver steatosis, highlighting potential therapeutic targets to prevent metabolic liver disease in individuals with prior intestinal inflammation.