Functional and metabolomic analyses of brown adipose tissue during cold-deacclimation reveal rapid N-acetylated amino acid adaptations

Non-shivering thermogenesis (NST) in brown adipose tissue (BAT) is rapidly activated in the cold but inactive at warm ambient temperatures. To elucidate the metabolic remodeling in BAT during recovery from cold exposure, mice were acclimated to 4°C for 7 days, then deacclimated at thermoneutrality (30°C) for 3-48 h. Cold-acclimated mice demonstrated high metabolic rates and food intake, which decreased immediately by ∼40% upon deacclimation. Uncoupled respiration decreased by 24 h, corresponding with gradual declines in mitochondrial protein content and UCP1 gene expression. Decreases in BAT mitochondrial content paralleled declines in protein content by 48 h of cold deacclimation. Metabolomic profiling revealed major alterations in amino acid, TCA cycle, glutathione, and purine metabolism pathways. Marked decreases in the abundance of N-acetylated amino acids in cold deacclimated mice corresponded with increased aminoacylase 1 (Acy1) expression. Together, results highlight the coordinated structural and metabolic remodeling of BAT mitochondria during thermogenesis and deactivation.