This study examined how brown adipose tissue (BAT) shapes the circulating metabolome by performing serum metabolomics and lipidomics in BAT-ablated mice and human cohorts with varying BAT activity, integrating data across serum, tissues, extracellular fluids, and conditioned media.
BAT was found to clear circulating branched-chain amino acids and triglycerides, and a cold-inducible metabolite — 3-hydroxystearic acid (3-OHSA) — was identified as a BAT-derived circulating signal that acts on the liver to reduce mitochondrial membrane potential and reactive oxygen species (ROS) production, thereby limiting hepatic oxidative stress.
Primarily preclinical (mouse BAT-ablation model); causal directionality in human cohorts is observational only; mechanism of 3-OHSA hepatic action is not fully resolved.
3-OHSA may serve as a non-invasive circulating biomarker of cold-activated BAT activity. The BAT-liver axis identified here could inform future therapeutic strategies targeting metabolic and oxidative stress-related liver disease.
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