Modulation of Adiponectin Receptors AdipoR1 and AdipoR2 by Phage Display-Derived Peptides in in vitro and in vivo Models

Crombez, Deborah; Delcambre, Sébastien; Nonclercq, Denis; Vander Elst, Luce; Laurent, Sophie; Cnop, Miriam; Muller, Robert; Burtea, Carmen

doi:10.1080/1061186X.2019.1710840

Article (Scientific journals)

Modulation of Adiponectin Receptors AdipoR1 and AdipoR2 by Phage Display-Derived Peptides in in vitro and in vivo Models

Crombez, Deborah; Delcambre, Sébastien; Nonclercq, Denis et al.

2020 • In Journal of Drug Targeting, 28 (7-8), p. 831-851

Peer Reviewed verified by ORBi

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https://hdl.handle.net/20.500.12907/10079

DOI
10.1080/1061186X.2019.1710840

PubMed
31888393

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Keywords :

[en] phage display; [en] type 2 diabetes; [en] peptide; [en] adiponectin; [en] obesity; [en] adiponectin receptors; [en] metabolic syndrome

Abstract :

[en] Type 2 diabetes (T2D) is often linked to metabolic syndrome, which assembles various risk factors related to obesity. Plasma levels of adiponectin are decreased in T2D and obese subjects. Aiming to develop a peptide able to bind adiponectin receptors and modulate their signalling pathways, a 12-amino acid sequence homologous in AdipoR1/R2 has been targeted by phage display with a linear 12-mer peptide library. The selected peptide P17 recognizes AdipoR1/R2 expressed by skeletal muscle, liver and pancreatic islets. In HepaRG and C2C12 cells, P17 induced the activation of AMPK (AMPKα-pT172) and the expression of succinate dehydrogenase and glucokinase; no cytotoxic effects were observed on HepaRG cells. In db/db mice, P17 promoted body weight and glycemia stabilization, decreased plasma triglycerides to the range of healthy mice and increased adiponectin (in high fat-fed mice) and insulin (in chow-fed mice) levels. It restored to the range of healthy mice the tissue levels and subcellular distribution of AdipoR1/R2, AMPKα-pT172 and PPARα-pS12. In liver, P17 reduced steatosis and apoptosis. The docking of P17 to AdipoR is reminiscent of the binding mechanism of adiponectin. To conclude, we have developed an AdipoR1/AdipoR2-targeted peptide that modulates adiponectin signalling pathways and has therapeutic relevance for T2D and obesity associated pathologies.

Research center :

CMMI - Centre de Recherche en Microscopie et Imagerie Médicale

Disciplines :

Endocrinology, metabolism & nutrition
Immunology & infectious disease
Pharmacy, pharmacology & toxicology
Biotechnology
Zoology
Chemistry

Author, co-author :

Crombez, Deborah

Delcambre, Sébastien

Nonclercq, Denis ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Histologie

Vander Elst, Luce ; Université de Mons > Faculté de Médecine et de Pharmacie > Service du Doyen de la Faculté de Médecine et Pharmacie

Laurent, Sophie ; Université de Mons > Faculté de Médecine et de Pharmacie > Service de Chimie générale, organique et biomédicale

Cnop, Miriam

Muller, Robert ; Université de Mons > Faculté de Médecine et de Pharmacie > Service du Doyen de la Faculté de Médecine et Pharmacie

Burtea, Carmen ; Université de Mons > Faculté de Médecine et de Pharmacie > Service de Chimie générale, organique et biomédicale

Language :

English

Title :

Modulation of Adiponectin Receptors AdipoR1 and AdipoR2 by Phage Display-Derived Peptides in in vitro and in vivo Models

Publication date :

15 August 2020

Journal title :

Journal of Drug Targeting

ISSN :

1061-186X

Publisher :

Taylor & Francis, United Kingdom

Volume :

Issue :

7-8

Pages :

831-851

Peer reviewed :

Peer Reviewed verified by ORBi

Research unit :

M108 - Chimie générale, organique et biomédicale
M118 - Histologie

Research institute :

R550 - Institut des Sciences et Technologies de la Santé
R100 - Institut des Biosciences

Name of the research project :

thèse co-financée Crombez - Fédération Wallonie Bruxelles

Available on ORBi UMONS :

since 30 December 2019

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