@misc{10481/78483, year = {2022}, month = {11}, url = {https://hdl.handle.net/10481/78483}, abstract = {Background The application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold. Methods This secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.gov ID: NCT03012113). We performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. Next, the intracellular lipolysis was blocked in mice (eighteen 10-week-old male wild-type mice C57BL/ 6J) using a small-molecule inhibitor of adipose triglyceride lipase (ATGL; Atglistatin), and mice were exposed to cold for a similar duration. The quantitative lipidomic profiling was assessed in-depth using the Lipidyzer platform. Findings In humans, cold exposure gradually increased circulating free fatty acids reaching a maximum at 60 min, and transiently decreased total triacylglycerols (TAGs) only at 30 min. A broad range of TAG species was initially decreased, in particular unsaturated and polyunsaturated TAG species with ≤5 double bonds, while after 120 min a significant increase was observed for polyunsaturated TAG species with ≥6 double bonds in humans. The mechanistic study in mice revealed that the cold-induced increase in polyunsaturated TAGs was largely prevented by blocking adipose triglyceride lipase. Interpretation We interpret these findings as that cold exposure feeds thermogenic tissues with TAG-derived fatty acids for combustion, resulting in a decrease of circulating TAG species, followed by increased hepatic production of polyunsaturated TAG species induced by liberation of free fatty acids stemming from adipose tissue.}, organization = {Netherlands CardioVascular Research Initiative: `the Dutch Heart Foundation}, organization = {Dutch Federation of University Medical Centers}, organization = {Netherlands Organization for Health Research and Development Royal Netherlands Academy of Sciences' CVON201720 GENIUS-II}, organization = {Fundacion Alfonso Martin Escudero}, organization = {Maria Zambrano - Ministerio de Universidades y la Union Europea -NextGenerationEU RR_C_2021_04}, organization = {Spanish Government FPU19/01609}, organization = {European Foundation for the Study of Diabetes (EFSD)}, organization = {NWO XOmics project 184.034.019}, publisher = {Elsevier}, keywords = {Cold}, keywords = {Desaturation}, keywords = {Fatty acid metabolism}, keywords = {Intracellular lipolysis}, keywords = {Long-chain polyunsaturated fatty acids}, title = {Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: A randomized cross-over trial}, doi = {10.1016/j.ebiom.2022.104349}, author = {Straat, Maaike E. and Jurado Fasoli, Lucas}, }