The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking

Open Biology - Tập 6 Số 4 - Trang 150272 - 2016
Ren Zhang1
1Ren Zhang [email protected] Google Scholar Find this author on PubMed

Tóm tắt

Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed–fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8–Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated.

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Tài liệu tham khảo

Eckel RH, 1989, Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases, N. Engl. J. Med, 320, 1060

Goldberg IJ, 1996, Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis, J. Lipid Res, 37, 693, 10.1016/S0022-2275(20)37569-6

10.1152/ajpendo.90920.2008

10.1016/j.bbalip.2014.03.013

10.1194/jlr.R200015-JLR200

10.1126/science.98.2531.19

10.1126/science.120.3114.399-a

10.1016/0020-711X(81)90177-4

10.1074/jbc.M401028200

10.1152/ajpendo.00349.2013

10.1172/JCI16751

10.2337/db07-1839

10.1073/pnas.121164498

10.2337/diabetes.50.5.1064

10.1194/jlr.R800085-JLR200

10.1074/jbc.270.21.12518

10.1001/jama.1991.03460070086049

10.1172/JCI118319

10.1016/j.cmet.2014.01.017

10.1016/j.cmet.2007.02.002

10.1016/j.cmet.2010.04.016

10.1161/ATVBAHA.109.186577

10.1016/j.jacl.2014.10.003

10.1194/jlr.M002717

10.1161/CIRCGENETICS.109.908905

10.1097/MOL.0b013e3281527914

10.1101/gad.209296.112

10.1097/MOL.0b013e32834d0b33

10.1210/en.2005-0476

10.1038/ng814

10.1538/expanim.55.27

10.1074/jbc.M203215200

10.1074/jbc.M302861200

10.1016/j.cmet.2007.07.009

10.1074/jbc.M807899200

10.1194/jlr.M054890

10.1073/pnas.1515374112

10.1042/bj3460603

10.1128/MCB.20.14.5343-5349.2000

10.1074/jbc.M004029200

10.1194/jlr.C200010-JLR200

10.1161/ATVBAHA.108.182147

10.1074/jbc.M403058200

10.1074/jbc.M307583200

10.1074/jbc.M113.497602

10.1074/jbc.M114.623769

10.1073/pnas.0604026103

10.1074/jbc.M808477200

10.1073/pnas.0705041104

10.7554/eLife.08428

10.1186/1472-6793-12-13

10.1056/NEJMoa1002926

10.1161/CIRCGENETICS.111.960674

10.1038/ng1984

10.1161/ATVBAHA.108.176917

Romeo S, 2009, Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans, J. Clin. Invest, 119, 70

10.1152/ajpendo.00084.2012

10.1016/j.bbrc.2012.07.038

10.1073/pnas.1217552109

10.1016/j.cell.2013.04.008

10.1093/nar/gku1071

10.1186/s12933-014-0133-8

10.1016/j.bbrc.2013.01.129

10.1038/nbt.1644

10.1073/pnas.1315292110

10.1038/srep18502

10.1016/j.bbrc.2012.12.025

10.1016/j.mce.2015.07.031

10.4161/auto.26126

10.1136/jmedgenet-2012-101461

10.1016/j.ajhg.2014.01.009

10.1038/nature09270

10.1038/srep05013

10.1155/2014/323407

10.2337/dc14-0602

10.1210/jc.2014-2300

10.1111/dme.12696

10.1507/endocrj.EJ14-0525

Gao T, 2015, Circulating betatrophin correlates with triglycerides and postprandial glucose among different glucose tolerance statuses: a case–control study, PLoS ONE, 10, e0133640, 10.1371/journal.pone.0133640

10.1210/jc.2013-4349

10.1530/EJE-14-0815

10.1371/journal.pone.0131171

10.1371/journal.pone.0136701

10.1111/pedi.12233

10.1007/s00125-013-3071-1

10.1007/s00125-014-3346-1

10.1210/jc.2014-1568

10.1186/s12933-016-0346-0

Calan M, Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome, Endocrine

10.1371/journal.pone.0147367

Pascual-Corrales E, Circulating ANGPTL8/betatrophin concentrations are increased after surgically induced weight loss, but not after diet-induced weight loss, Obes. Surg

10.1186/s12933-015-0326-9

10.1186/s12933-015-0324-y

10.1210/JC.2015-1595

10.1002/oby.21038

10.1007/s00125-014-3208-x

10.1042/bj0930010C

10.1074/jbc.M200325200

Ben-Zeev O, 1983, Evidence for independent genetic regulation of heart and adipose lipoprotein lipase activity, J. Biol. Chem, 258, 13 632, 10.1016/S0021-9258(17)43962-7

10.1152/ajpendo.00634.2006

10.1016/j.cmet.2016.01.005

10.1194/jlr.M900145-JLR200

10.1073/pnas.1513872112

10.3109/09513590.2015.1056142

Mooradian AD, 2009, Dyslipidemia in type 2 diabetes mellitus, Nat. Clin. Pract. Endocrinol. Metab, 5, 150

Lek M, Analysis of protein-coding genetic variation in 60 706 humans, bioRxiv

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