A high-resolution, sex-stratified atlas of transcriptional and alternative splicing dynamics in the fasting mouse liver.

Here we present a high-resolution transcriptomic atlas of the fasting mouse liver, profiling both male and female C57BL/6 mice every 4 hours across a 36-hour fast initiated at a defined circadian time. Using an integrated framework combining high-resolution time-series analysis with stringent statistical filtering, we identify 2,995 genes organised into eight kinetically distinct clusters that collectively delineate a phased transcriptional transition from acute metabolic remodelling to prolonged nutrient deprivation.

Contrary to prior reports, fasting amplifies rather than diminishes circadian transcription, increasing the number of rhythmically expressed genes from 727 to 1,233—indicative of a clock re-gearing rather than clock disruption. Extending our analysis to exon-level quantification reveals that differential exon usage constitutes an independent regulatory layer, targeting processes not captured by transcript abundance alone, including SAM metabolism, ferroptosis and mRNA processing.