ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure

W. Dijk, M. Heine, L. Vergnes, M.R. Boon, G. Schaart, Matthijs Hesselink, K. Reue, Wouter van Marken Lichtenbelt, G. Olivecrona, P.C. Rensen, J. Heeren, S. Kersten

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Abstract

Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.
Original languageEnglish
Article numbere08428
Number of pages23
JournalElife
Volume4
DOIs
Publication statusPublished - 17 Oct 2015

Keywords

  • ACTIVATED PROTEIN-KINASE
  • LIPOPROTEIN-LIPASE
  • FATTY-ACIDS
  • EXPRESSION
  • TARGET
  • PLASMA
  • P300
  • GENE
  • PHOSPHORYLATION
  • DEFICIENCY

Cite this

Dijk, W., Heine, M., Vergnes, L., Boon, M. R., Schaart, G., Hesselink, M., Reue, K., van Marken Lichtenbelt, W., Olivecrona, G., Rensen, P. C., Heeren, J., & Kersten, S. (2015). ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure. Elife, 4, [e08428]. https://doi.org/10.7554/eLife.08428