Characterisation of the circulating and tissue-specific alterations to the lipidome in response to moderate and major cold stress in mice

This study analysed the effects of 24 hours of cold stress (22°C or 5°C vs. mice maintained at 30°C) on the plasma, brown adipose tissue (BAT), subcutaneous (SubQ) and epididymal (Epi) white adipose tissue (WAT), liver, and skeletal muscle lipidome of mice. Using mass spectrometry-lipidomics 624 lipid species were detected, of which 239 were significantly altered in plasma, 134 in BAT, and 51 in the liver. In plasma, acylcarnitines and free fatty acids were markedly increased at 5°C. Plasma triacylglycerols (TGs) were reduced at 22°C and 5°C. We also identified ether lipids as a novel, cold-induced lipid class. In BAT, TGs were the principal lipid class affected by cold stress, being significantly reduced at both 22°C and 5°C. Interestingly, while BAT TG species were uniformly affected at 5°C, at 22°C we observed species-dependent effects, with TGs containing longer and more unsaturated fatty acids particularly sensitive to the effects of cold. In the liver, TGs were the most markedly affected lipid class, increasing in abundance at 5°C. TGs containing longer and more unsaturated fatty acids accumulated to a greater degree. Our work demonstrates: (1) Acute exposure to moderate (22°C) cold stress alters the plasma and BAT lipidome; although this effect is markedly less pronounced than at 5°C. (2) Cold stress at 5°C dramatically alters the plasma lipidome, with ether lipids identified as a novel lipid class altered by cold exposure. (3) That cold-induced alterations in liver and BAT TG levels are not uniform, with changes being influenced by acyl chain composition.