ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
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ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure. / Dijk, Wieneke; Heine, Markus; Vergnes, Laurent; Boon, Mariëtte R; Schaart, Gert; Hesselink, Matthijs Kc; Reue, Karen; van Marken Lichtenbelt, Wouter D; Olivecrona, Gunilla; Rensen, Patrick Cn; Heeren, Joerg; Kersten, Sander.
In: ELIFE, Vol. 4, 17.10.2015.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
AU - Dijk, Wieneke
AU - Heine, Markus
AU - Vergnes, Laurent
AU - Boon, Mariëtte R
AU - Schaart, Gert
AU - Hesselink, Matthijs Kc
AU - Reue, Karen
AU - van Marken Lichtenbelt, Wouter D
AU - Olivecrona, Gunilla
AU - Rensen, Patrick Cn
AU - Heeren, Joerg
AU - Kersten, Sander
PY - 2015/10/17
Y1 - 2015/10/17
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.08428
DO - 10.7554/eLife.08428
M3 - SCORING: Journal article
C2 - 26476336
VL - 4
JO - ELIFE
JF - ELIFE
SN - 2050-084X
ER -