Ghrelin and LEAP-2: Rivals in Energy Metabolism

被引：50

作者：

Al-Massadi, Omar ^{[1
,2
]}

Mueller, Timo ^{[3
,4
,5
]}

Tschoep, Matthias ^{[3
,4
,5
]}

Dieguez, Carlos ^{[1
,2
]}

Nogueiras, Ruben ^{[1
,2
]}

机构：

[1] Univ Santiago de Compostela, Inst Invest Sanitaria, CIMUS, Dept Physiol, Santiago De Compostela 15782, Spain

[2] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago 15706, Spain

[3] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Munich, Germany

[4] German Ctr Diabet Res DZD, Neuherberg, Germany

[5] Tech Univ Munich, Div Metab Dis, Munich, Germany

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2018年 / 39卷 / 08期

关键词：

DES-ACYL GHRELIN; GROWTH-HORMONE-SECRETION; FOOD-INTAKE; DOUBLE-BLIND; WEIGHT-LOSS; GASTRIC BYPASS; PEPTIDE; APPETITE; ADIPOSITY; OBESITY;

D O I：

10.1016/j.tips.2018.06.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Liver-expressed antimicrobial peptide 2 (LEAP-2), the endogenous noncompetitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a), was recently identified as a key endocrine factor regulating systemic energy metabolism. This antagonist impairs the ability of ghrelin to activate GHSR1a and diminishes ghrelin-induced Ca2+ release in vitro. The physiological relevance of the molecular LEAP-2-GHSR1a interaction was subsequently demonstrated in vivo. LEAP-2 is therefore a promising therapeutic target in the treatment of obesity and other metabolic diseases. Here, we discuss not only the current understanding of LEAP-2 in metabolic regulation, but also the potential of this peptide in the treatment of obesity and other diseases that involve dysregulation of the ghrelin system.

引用

页码：685 / 694

页数：10

共 62 条

[1] Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite [J].

Abizaid, Alfonso ;

Liu, Zhong-Wu ;

Andrews, Zane B. ;

Shanabrough, Marya ;

Borok, Erzsebet ;

Elsworth, John D. ;

Roth, Robert H. ;

Sleeman, Mark W. ;

Picciotto, Marina R. ;

Tschop, Matthias H. ;

Gao, Xiao-Bing ;

Horvath, Tamas L. .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (12) :3229-3239

[2] Current Understanding of the Hypothalamic Ghrelin Pathways lncucinc Appetite anc Adiposity [J].

Al Massadi, Omar ;

Lopez, Miguel ;

Tschop, Matthias ;

Dieguez, Carlos ;

Nogueiras, Ruben .

TRENDS IN NEUROSCIENCES, 2017, 40 (03) :167-180

[3]

Al Massadi O, 2014, CURR DRUG METAB, V15, P398

[4] FOOD INTAKE AND EATING BEHAVIOR AFTER BARIATRIC SURGERY [J].

Al-Najim, Werd ;

Docherty, Neil G. ;

le Roux, Carel W. .

PHYSIOLOGICAL REVIEWS, 2018, 98 (03) :1113-1141

[5] UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals [J].

Andrews, Zane B. ;

Liu, Zhong-Wu ;

Walllingford, Nicholas ;

Erion, Derek M. ;

Borok, Erzsebet ;

Friedman, Jeffery M. ;

Tschop, Matthias H. ;

Shanabrough, Marya ;

Cline, Gary ;

Shulman, Gerald I. ;

Coppola, Anna ;

Gao, Xiao-Bing ;

Horvath, Tamas L. ;

Diano, Sabrina .

NATURE, 2008, 454 (7206) :846-851

[6] Glucose and Weight Control in Mice with a Designed Ghrelin O-Acyltransferase Inhibitor [J].

Barnett, Brad P. ;

Hwang, Yousang ;

Taylor, Martin S. ;

Kirchner, Henriette ;

Pfluger, Paul T. ;

Bernard, Vincent ;

Lin, Yu-yi ;

Bowers, Erin M. ;

Mukherjee, Chandrani ;

Song, Woo-Jin ;

Longo, Patti A. ;

Leahy, Daniel J. ;

Hussain, Mehboob A. ;

Tschoep, Matthias H. ;

Boeke, Jef D. ;

Cole, Philip A. .

SCIENCE, 2010, 330 (6011) :1689-1692

[7] The Effects of Vertical Sleeve Gastrectomy in Rodents Are Ghrelin Independent [J].

Chambers, Adam P. ;

Kirchner, Henriette ;

Wilson-Perez, Hilary E. ;

Willency, Jill A. ;

Hale, John E. ;

Gaylinn, Bruce D. ;

Thorner, Michael O. ;

Pfluger, Paul T. ;

Gutierrez, Jesus A. ;

Tschoep, Matthias H. ;

Sandoval, Darleen A. ;

Seeley, Randy J. .

GASTROENTEROLOGY, 2013, 144 (01) :50-U124

[8] Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials [J].

Christensen, Robin ;

Kristensen, Pernelle Kruse ;

Bartels, Else Marie ;

Blidda, Henning ;

Astrup, Arne .

LANCET, 2007, 370 (9600) :1706-1713

[9] Ghrelin mediates stress-induced food-reward behavior in mice [J].

Chuang, Jen-Chieh ;

Perello, Mario ;

Sakata, Ichiro ;

Osborne-Lawrence, Sherri ;

Savitt, Joseph M. ;

Lutter, Michael ;

Zigman, Jeffrey M. .

JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (07) :2684-2692

[10] Gut-Brain Cross-Talk in Metabolic Control [J].

Clemmensen, Christoffer ;

Mueller, Timo D. ;

Woods, Stephen C. ;

Berthoud, Hans-Rudolf ;

Seeley, Randy J. ;

Tschoep, Matthias H. .

CELL, 2017, 168 (05) :758-774

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