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SHR Neuro Cancer Cardio Lipid Metab Microb

Straat, ME; Jurado-Fasoli, L; Ying, Z; Nahon, KJ; Janssen, LGM; Boon, MR; Grabner, GF; Kooijman, S; Zimmermann, R; Giera, M; Rensen, PCN; Martinez-Tellez, B.
Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: A randomized cross-over trial.
EBioMedicine. 2022; 86: 104349 Doi: 10.1016/j.ebiom.2022.104349 [OPEN ACCESS]
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Co-authors Med Uni Graz
Grabner Gernot
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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. FUNDING: This work was supported by the Netherlands CardioVascular Research Initiative: 'the Dutch Heart Foundation, 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 Fundación Alfonso Martin Escudero and by a Maria Zambrano fellowship by the Ministerio de Universidades y la Unión 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.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Humans - administration & dosage
Male - administration & dosage
Mice - administration & dosage
Adipose Tissue - metabolism
Cross-Over Studies - administration & dosage
Fatty Acids, Nonesterified - blood, metabolism
Lipase - metabolism
Lipolysis - administration & dosage
Mice, Inbred C57BL - administration & dosage
Triglycerides - blood, metabolism
Cold Temperature - administration & dosage

Find related publications in this database (Keywords)
Cold
Desaturation
Fatty acid metabolism
Intracellular lipolysis
Long-chain polyunsaturated fatty acids
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