Cold-Induced Lipidomic Remodelling Is Associated With Brown Adipose Tissue Mean Radiodensity in Humans

Cold exposure activates brown adipose tissue (BAT) and promotes thermogenic and metabolic adaptations. While BAT activation has been linked to improved cardiometabolic health, how acute cold exposure reshapes the circulating lipidome in humans remains incompletely understood.

We profiled 656 plasma lipid species across 14 subclasses in 58 young sedentary adults (72% women) before and during a 2-h cold exposure using mass spectrometry-based lipidomics and assessed their associations with BAT volume, activity and mean radiodensity.

Here, we demonstrate that acute cold exposure increased circulating membrane-associated phospholipids while decreasing triacylglycerol (TG) and phosphatidylethanolamine (PE) species, indicating a redistribution of lipid classes towards structural and signalling lipids. These lipid alterations were structurally selective, with both phospholipids and TG showing the largest shifts among species with shorter and less unsaturated acyl chains. Notably, cold-induced reductions in circulating TG species were negatively correlated with BAT mean radiodensity, linking systemic lipid remodelling to BAT activation.

These findings define a distinct lipidomic signature of acute cold exposure in humans and suggest that even short-term BAT activation is associated with coordinated remodelling of circulating lipid networks. This lipid remodelling may reflect enhanced BAT lipid utilisation and contribute to the cardiometabolic benefits associated with cold exposure. Future studies are warranted in more diverse populations, including older individuals and those with obesity or type 2 diabetes, in whom BAT activity and lipid metabolism differ substantially.