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

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Dijk, Wieneke | Heine, Markus | Vergnes, Laurent | Boon, Mariëtte | Schaart, Gert | Hesselink, Matthijs Kc | Reue, Karen | van Marken Lichtenbelt, Wouter | Olivecrona, Gunilla | Rensen, Patrick Cn | Heeren, Joerg | Kersten, Sander

Edité par CCSD ; eLife Sciences Publication -

International audience. 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.

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