Abstract 535: Acute sleep deprivation reprograms metabolic and mitochondrial pathways linked to cancer risk.

Abstract Sleep deprivation is common and has been linked to elevated cancer risk, yet the immediate mammalian responses that connect acute sleep loss to cancer remain unclear. We asked whether a single 5-hour bout of acute sleep deprivation (ASD) reprograms metabolic and mitochondrial pathways across organs that govern whole-body energetics in a mouse model. Twelve-week C57BL/6 female mice underwent ASD or ad lib sleep; liver, hippocampus, prefrontal cortex, and gastrocnemius were collected immediately and profiled by RT-qPCR for energy sensing (AMPK), glucose transport (GLUT3), mitochondrial dynamics (DRP1/MFN1/OPA1), and hepatic lipid/cholesterol handling (ABCA1/SCARB1/apolipoproteins). ASD triggered rapid, tissue-selective remodeling: AMPK/GLUT3 and mitochondrial-dynamics transcripts rose in brain regions, while hepatic cholesterol transport and apolipoproteins were altered; however skeletal muscle showed minimal change. These coordinated shifts map to cancer-relevant processes—deregulated cellular energetics, mitochondrial quality control/redox, and sterol flux that shapes membrane signaling and tissue inflammation, positioning sleep state as a modifiable, system-wide determinant of cancer susceptibility and progression. Ongoing work will examine whether repeated ASD or sleep restoration tunes these pathways and related tumor-relevant endpoints. Citation Format: Behzad Varamini, Harrison Kim, Priscilla Kim, Madeline Lange, Stephanie Zeng, Jennifer Tudor. Acute sleep deprivation reprograms metabolic and mitochondrial pathways linked to cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 535.