Two Stages of Dynamic Metabolic and Transcriptomic Remodeling During the Adaptation to Caloric Restriction in Male C57BL/6J

in iWAT, whose structural integration is established prior to the broader transcriptional remodeling observed at later timepoints. Functional annotation indicates the hepatic hub network is enriched for mitochondrial bioenergetics and FOXO/TP53-mediated transcription, while the iWAT hub network exhibits a bifurcated enrichment spanning ribosomal biosynthesis and immune-regulatory signaling. Although these tissues exhibit distinct transcriptional profiles, projecting both datasets onto a shared phenotypic eigenspace reveals a unified systemic response; as CR is maintained, dynamically regulated transcripts in both liver and iWAT converge on an adiponectin-coupled state. Ultimately, the identification of adiponectin as an integrative signal coordinating chronic adaptation across metabolically distinct tissues delineates the temporal sequence of early CR adaptation; furthermore, it establishes a mechanistic framework defining how early molecular and physiological shifts converge to achieve steady-state metabolic homeostasis.