Cold-Induced Thermogenesis Increases Acetylation on the Brown Fat Proteome and Metabolome

ABSTRACT Stimulating brown adipose tissue (BAT) energy expenditure could be a therapy for obesity and related metabolic diseases. Achieving this requires a systems-level understanding of the biochemical underpinnings of thermogenesis. To identify novel metabolic features of active BAT, we measured protein abundance, protein acetylation, and metabolite levels in BAT isolated from mice living in their thermoneutral zone or in colder environments. We find that the enzymes which synthesize lipids from cytosolic acetyl-coA are among the most robustly increased proteins after cold acclimation, consistent with recent studies highlighting the importance of anabolic de novo lipogenesis in BAT. In addition, many mitochondrial proteins are hyperacetylated by cold acclimation, including several sites on UCP1, which may have functional relevance. Metabolomics analysis further reveals cold-dependent increases to acetylated carnitine and several amino acids. This BAT multi-omics resource highlights widespread proteomic and metabolic changes linked to acetyl-CoA synthesis and utilization that may be useful in unraveling the remarkable metabolic properties of active BAT.