Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: a randomized cross-over trial

Straat, M.E.; Jurado-Fasoli, L.; Ying, Z.X.; Nahon, K.J.; Janssen, L.G.M.; Boon, M.R.; ... ; Martinez-Telleza, B. (2022)

Article / Letter to editor

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 mecha-nistic 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. Funding: This work was supported by the Netherlands CardioVascular Research Initiative: 'the Dutch Heart Foun-dation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences' [CVON2017-20 GENIUS-II] to Patrick C.N. Rensen. Borja Martinez-Tellez is supported by individual postdoctoral grant from the Fundacion Alfonso Martin Escudero and by a Maria Zambrano fellowship by the Ministerio de Universidades y la Union Europea - NextGenerationEU (RR_C_2021_04). Lucas Jurado-Fasoli was supported by an individual pre-doctoral grant from the Spanish Ministry of Education (FPU19/01609) and with an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes (EFSD). Martin Giera was partially supported by NWO XOmics project #184.034.019.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 2022;86: Published https://doi.org/10. 1016/j.ebiom.2022. 104349

• Cold
• Desaturation
• Fatty acid metabolism
• Intracellular lipolysis
• Long-chain polyunsaturated fatty acids

• All authors: Straat, M.E.; Jurado-Fasoli, L.; Ying, Z.X.; Nahon, K.J.; Janssen, L.G.M.; Boon, M.R.; Grabner, G.F.; Kooijman, S.; Zimmermann, R.; Giera, M.; Rensen, P.C.N.; Martinez-Telleza, B.
• Date: 2022-12-01
• Journal: EBioMedicine
• Volume: 86
• DOI: doi:10.1016/j.ebiom.2022.104349