A groundbreaking study published in Acta Pharmaceutica Sinica B has revealed that sleep fragmentation associated with diabetes can cause lasting damage to both the liver and heart, highlighting a critical link between sleep disorders and cardiovascular disease (CVD).
The research uncovers a previously unexplored mechanism by which disrupted sleep contributes to nonalcoholic fatty liver disease (NAFLD) and, subsequently, to heart failure. While NAFLD is already recognized as a major risk factor for CVD, this study is the first to provide compelling evidence that liver damage induced by sleep fragmentation plays a direct role in cardiovascular deterioration.
According to the findings, sleep fragmentation (SF) results in severe liver abnormalities, including fat accumulation (steatosis) and oxidative stress, alongside structural and functional damage to the heart. Alarmingly, these adverse effects persisted even after two weeks of normal sleep, suggesting that SF leaves a “memory” of damage that continues to affect the organs.
At the core of this phenomenon is the liver’s elevated expression of NADPH oxidase 4 (NOX4), which the study identifies as the primary driver of SF-induced pathology. The researchers found that SF increases acetylation of histone H3 lysine 27 (H3K27ac) at the promoter region of the Nox4 gene, thereby enhancing its expression — an effect that remains even after sleep patterns are normalized.
The study further details how circadian rhythm misalignment exacerbates liver injury through disruption of SIRT1, a gene regulated by the clock protein BMAL1. This molecular cascade leads to sustained liver dysfunction and contributes to ongoing cardiac damage.
Crucially, the researchers demonstrated that both genetic manipulation and pharmacological intervention can mitigate these effects. By either suppressing NOX4 or boosting SIRT1 activity — through agents such as GLX351322 and resveratrol, respectively — the team was able to reverse epigenetic changes, lower Nox4 expression, and significantly improve liver and heart health.
“These findings shed light on how diabetes-related sleep disturbances can cause long-term organ damage,” the authors concluded. “They also suggest promising therapeutic strategies for protecting the heart by targeting liver-based memory of sleep disruption.”
The study offers a new avenue for understanding and treating CVD in diabetic patients suffering from poor sleep, signaling an urgent need for further clinical exploration.
Related topics:
Study Links Poor Oral Health to Increased Pain and Migraines in Women
Harnessing Stress for Productivity Without Losing Empathy
Sleep Boosts Long-Term Memory for Life Events
