Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans

Anna Borup, Ida Donkin, Mariëtte R Boon, Martin Frydland, Borja Martinez-Tellez, Annika Loft, Sune H Keller, Andreas Kjaer, Jesper Kjaergaard, Christian Hassager, Romain Barrès, Patrick C N Rensen, Christina Christoffersen*

*Corresponding author for this work


The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (β: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (β: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.

Original languageEnglish
Article number18753
JournalScientific Reports
Issue number1
Pages (from-to)18753
Publication statusPublished - 5 Nov 2022


  • Animals
  • Humans
  • Adipose Tissue, Brown/metabolism
  • Apolipoproteins M/metabolism
  • Lysophospholipids/metabolism
  • Positron Emission Tomography Computed Tomography
  • Sphingosine/metabolism


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