"Targeting the clock: New study reveals how a circadian rhythm protein fuels inflammation by shuttling a metabolic enzyme into the nucleus."
Research published on June 9, 2026, in Cell Reports has identified a molecular mechanism by which the circadian clock protein BMAL1 promotes inflammation in immune cells. The study was conducted by Akito Tsuruta, Naoya Matsunaga, Satoru Koyanagi, and Shigehiro Ohdo from Kyushu University.
Mechanism of Action
According to the study, BMAL1 binds to multi-functional protein 2 (MFP2), a fatty acid oxidation enzyme, and transports it into the cell nucleus. Inside the nucleus, MFP2 increases levels of acetyl-CoA, a molecule that facilitates the acetylation of the protein p65. This acetylation activates NF-κB, a transcription factor that promotes the expression of pro-inflammatory genes. Researchers report that BMAL1 drives macrophages toward a pro-inflammatory (M1) state through this process.
Circadian Fluctuation
Nuclear MFP2 levels were observed to fluctuate in a circadian manner, reaching peak concentration when BMAL1 levels are highest.
Animal Model Findings
In mouse models, macrophage-specific BMAL1 deficiency resulted in reduced inflammation and suppressed the formation of liver tumors induced by the chemical carcinogen diethylnitrosamine.
Background Context
The circadian clock synchronizes biological functions including sleep, metabolism, and immune activity. Macrophages can exist in a pro-inflammatory (M1) state or an anti-inflammatory (M2) state. Disruption of the M1/M2 balance is associated with chronic inflammation and diseases such as cancer, liver disease, diabetes, and autoimmune disorders.
Implications and Future Research
The researchers suggest that targeting nuclear MFP2 or timing drug administration to coincide with peak nuclear MFP2 levels could lead to new treatments for chronic inflammatory diseases and cancer. The authors plan to validate the mechanism in human cells and explore timed drug administration in inflammatory disease and cancer models.