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Chen-Roetling, J.

Publications and source records attributed to Chen-Roetling, J..

2 recordsLinked to original sources

Sleep regulates hepatic neutrophil trafficking by modulating uric acid metabolism via sympathetic nervous system activity

Sleep is essential for survival and serves as a key regulator of metabolic and immune function. Sleep loss is strongly associated with metabolic stress and liver inflammation. The mechanisms linking sleep disruption to hepatic metabolic inflammation (metaflammation) remain poorly defined. Here, we show that sleep loss triggers metaflammation through a sympathetic-metabolic-immune axis. Acute sleep deprivation (SD) activates hepatic sympathetic signaling, leading to increased uric acid (UA) synthesis driven by enhanced expression and activity of xanthine dehydrogenase/xanthine oxidase (XDH/XO) in the liver. Elevated UA, acting as an immune-stimulatory metabolic signal, promotes hepatic neutrophil recruitment and pro-inflammatory cytokine production, a response that is rapidly reversed upon sleep recovery. Our findings identify sleep-dependent sympathetic control of hepatic UA metabolism as a driver of acute liver inflammation and reveal how acute sleep loss reprograms liver immune-metabolic homeostasis.

neuroscience↗

Heat Shock Factor 1 Governs Sleep-Wake Cycles Across Species

Heat Shock Factor 1 (HSF1) is a critical transcription factor for cellular proteostasis, but its role in sleep regulation remains unexplored. We demonstrate that nuclear HSF1 levels in the mouse brain fluctuate with sleep-wake cycles, increasing during extended wakefulness and decreasing during sleep. Using CUT&RUN and RNA-seq, we identified HSF1-regulated transcriptional changes involved in synaptic organization, expanding its known functions beyond traditional heat shock responses. Both systemic and brain-specific Hsf1 knockout mice exhibit altered sleep homeostasis, including increased delta power after sleep deprivation and upregulation of sleep-related genes. However, these knockouts struggle to maintain sleep due to disrupted synaptic organization. In Drosophila, knockout of HSF1s ortholog results in fragmented sleep patterns, suggesting a conserved role for HSF1 in sleep regulation across species. Our findings reveal a novel molecular mechanism underlying sleep regulation and offer potential therapeutic targets for sleep disturbances.

neuroscience↗