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

被引：123

作者：

Dijk, Wieneke ^{[1
]}

Heine, Markus ^{[2
]}

Vergnes, Laurent ^{[3
,4
]}

Boon, Mariette R. ^{[5
,6
]}

Schaart, Gert ^{[7
]}

Hesselink, Matthijs K. C. ^{[7
]}

Reue, Karen ^{[3
,4
]}

Lichtenbelt, Wouter D. van Marken ^{[8
]}

Olivecrona, Gunilla ^{[9
]}

Rensen, Patrick C. N. ^{[5
,6
]}

Heeren, Joerg ^{[2
]}

Kersten, Sander ^{[1
]}

机构：

[1] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, NL-6700 AP Wageningen, Netherlands

[2] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Hamburg, Germany

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA

[5] Leiden Univ, Med Ctr, Dept Med, Div Endocrinol, Leiden, Netherlands

[6] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands

[7] Maastricht Univ, Dept Human Movement Sci, NL-6200 MD Maastricht, Netherlands

[8] Maastricht Univ, Med Ctr, Dept Human Biol, NL-6200 MD Maastricht, Netherlands

[9] Umea Univ, Dept Med Biosci Physiol Chem, Umea, Sweden

来源：

ELIFE | 2015年 / 4卷

关键词：

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

D O I：

10.7554/eLife.08428

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

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. DOI:10.7554/eLife.08428.001

引用

页数：23

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