Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

被引：120

作者：

Catoire, MilSNe ^{[1
]}

Alex, Sheril ^{[1
]}

Paraskevopulos, Nicolas ^{[1
]}

Mattijssen, Frits ^{[1
]}

Evers-van Gogh, Inkie ^{[2
]}

Schaart, Gert ^{[3
]}

Jeppesen, Jacob ^{[5
]}

Kneppers, Anita ^{[1
]}

Mensink, Marco ^{[1
]}

Voshol, Peter J. ^{[6
]}

Olivecrona, Gunilla ^{[7
]}

Tan, Nguan Soon ^{[8
]}

Hesselink, Matthijs K. C. ^{[6
]}

Berbee, Jimmy F. ^{[9
,10
]}

Rensen, Patrick C. N. ^{[9
,10
]}

Kalkhoven, Eric ^{[2
]}

Schrauwen, Patrick ^{[4
]}

Kersten, Sander ^{[1
]}

机构：

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

[2] Univ Med Ctr Utrecht, Dept Metab Dis, NL-3584 EA Utrecht, Netherlands

[3] Maastricht Univ, Med Ctr, Dept Human Movement Sci, NL-6200 MD Maastricht, Netherlands

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

[5] Univ Copenhagen, Sect Mol Physiol, Dept Nutr Exercise & Sports, DK-2200 Copenhagen, Denmark

[6] Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England

[7] Umea Univ, Dept Med Biosci Physiol Chem, SE-90187 Umea, Sweden

[8] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore

[9] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands

[10] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 11期

关键词：

HUMAN SKELETAL-MUSCLE; ANGIOPOIETIN-LIKE PROTEIN-4; LIPOPROTEIN-LIPASE; ADIPOSE-TISSUE; INSULIN-RESISTANCE; POSTPRANDIAL TRIACYLGLYCEROL; ENDURANCE EXERCISE; IN-VIVO; EXPRESSION; RECEPTOR;

D O I：

10.1073/pnas.1400889111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise encodes angiopoietin-like 4 (ANGPTL4), an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. Using a combination of human, animal, and in vitro data, we show that induction of ANGPTL4 in nonexercising muscle is mediated by elevated plasma free fatty acids via peroxisome proliferator-activated receptor-delta, presumably leading to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles. Our data suggest that nonexercising muscle and the local regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing lipid homeostasis during exercise.

引用

页码：E1043 / E1052

页数：10

共 52 条

[1]

ANGPTL4 is produced by entero-endocrine cells in the human intestinal tract [J].