Inside nearly every cell of the body ticks an invisible clock, and Kyushu University researchers have just discovered that it has a surprisingly direct hand in inflammation—and potentially in cancer itself. The circadian clock protein BMAL1, which governs everything from when we sleep to how our immune system responds to threat, doesn't simply regulate inflammation through the usual genetic switches. Instead, it physically transports a fatty acid-processing enzyme into the nucleus, where it orchestrates a cascade of inflammatory signals. The finding, published in Cell Reports in June 2026, opens a new door to understanding how our body's daily rhythms shape our vulnerability to disease.
The problem at the heart of this discovery is one of balance. When the body encounters injury or infection, immune cells called macrophages spring into action, shifting between two states: a pro-inflammatory M1 state that promotes the initial response, and an anti-inflammatory M2 state that resolves inflammation and repairs tissue. When this balance breaks down, chronic inflammation can develop—a condition linked to cancer, liver disease, diabetes, and autoimmune disorders. Understanding what tips the scales toward chronic inflammation has long been a puzzle. Now, a team led by Lecturer Akito Tsuruta and Professor Shigehiro Ohdo at Kyushu University's Faculty of Pharmaceutical Sciences has illuminated a crucial piece of that puzzle.
The researchers began with macrophage-specific BMAL1-deficient mice—animals engineered to lack the protein in their immune cells—and exposed them to diethylnitrosamine, a chemical carcinogen that triggers liver inflammation and tumor growth. The results were striking. Normal mice developed a marked surge in pro-inflammatory M1 macrophages and elevated inflammatory signals. But the BMAL1-deficient mice showed significantly reduced inflammation and suppressed liver tumor development. This suggested that BMAL1 itself was driving the dangerous pro-inflammatory shift.
The mechanism turns out to be elegantly intricate. Using mass spectrometry to map protein interactions in the cell nucleus, Tsuruta's team discovered that BMAL1 binds to multi-functional protein 2 (MFP2), an enzyme usually confined to compartments called peroxisomes, and physically escorts it into the nucleus. Once there, MFP2 raises levels of acetyl-CoA, a molecule that chemically modifies key proteins including p65—a component of the transcription factor NF-κB, the master switch for inflammatory genes. This acetylation flips NF-κB into its active state, pushing macrophages toward the pro-inflammatory M1 state.
What makes this discovery particularly striking is its rhythmic dimension. Nuclear MFP2 levels rise and fall according to the time of day, fluctuating in sync with BMAL1 levels. In control mice, nuclear MFP2 peaked during periods when BMAL1 was highest; in BMAL1-deficient mice, this daily rhythm vanished. This opens a tantalizing possibility: inflammation itself might have a time-of-day signature that could be exploited therapeutically.
"We discovered a fundamentally new concept that the circadian clock controls inflammation not only through direct transcriptional regulation but also through nuclear lipid metabolism," Tsuruta explained. The findings suggest that future treatments could target nuclear MFP2 specifically and time drug delivery to optimal hours of the day—a strategy that could enhance therapeutic efficacy while minimizing side effects. As researchers move toward validating this mechanism in human cells, the promise is clear: understanding the body's clock may unlock new ways to fight inflammation and the diseases it fuels.