2026-06-11 九州大学
体内時計タンパク質BMAL1がペルオキシソーム酵素であるMFP2を細胞核内に輸送し、そこで産生されるアセチルCoAがNF-κBの活性化を介してマクロファージの炎症を促進することを発見しました。
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1500
- https://www.cell.com/cell-reports-physical-science/fulltext/S2211-1247(26)00558-9
The circadian clock component BMAL1 enhances macrophage inflammation by nuclear translocation of peroxisomal β-oxidation enzyme MFP2
Akito Tsuruta ∙ Nodoka Hirao ∙ Megumi Shibata ∙ … ∙ Naoya Matsunaga ∙ Satoru Koyanagi ∙ Shigehiro Ohdo
Cell Reports Published:June 9, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117480
Highlights
- Macrophage Bmal1 ablation inhibits carcinogen-induced liver inflammation and tumorigenesis
- Peroxisomal β-oxidation enzymes are localized in nucleus
- BMAL1 transports multifunctional protein 2 into nucleus in circadian manner
- Nuclear multifunctional protein 2 enhances inflammation through acetylation of p65
Summary
The circadian clock regulates diverse immune functions, yet the role of clock components in macrophage inflammation remains controversial, with both pro- and anti-inflammatory effects reported. Here, we identify a previously unrecognized mechanism by which the core circadian clock component BMAL1 enhances the inflammatory response of macrophages through the nuclear translocation of the peroxisomal β-oxidation enzyme multi-functional protein 2 (MFP2). BMAL1 drives MFP2 accumulation in the nucleus, where MFP2 contributes to acetyl-CoA production and acetylation of the NF-κB subunit p65, thereby facilitating M1 polarization and inflammatory chemokine expression. Nuclear MFP2 levels oscillate in a diurnal manner in the liver, but this rhythmicity is abolished in Bmal1-deficient mice. Macrophage-specific deletion of BMAL1 alleviates diethylnitrosamine-induced hepatic inflammation and tumorigenesis, concomitant with reduced inflammatory gene expression. These findings uncover a BMAL1-dependent nuclear metabolic pathway that links circadian regulation of macrophage inflammation and suggest that targeting nuclear MFP2 may offer a therapeutic approach for inflammatory diseases and tumorigenesis.
