Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance.

M. Maris 1 L. Overbergh 1, * C. Gysemans 1 A. Waget 2, 3 A. K. Cardozo 2, 3 E. Verdrengh 1 J. P. M. Cunha 1 T. Gotoh 4 M. Cnop 3, 5 D. L. Eizirik 3 R. Burcelin 2 C. Mathieu 1
* Auteur correspondant
1 LEGENDO - Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven
2 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
3 ULB - Laboratory of Experimental Medicine, Université Libre de Bruxelles
4 Department of School Health, Faculty of Education & Department of Molecular Genetics, Kumamoto University, Kumamoto
5 ULB - Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles
Abstract : AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress has been implicated in the development of type 2 diabetes, via effects on obesity, insulin resistance and pancreatic beta cell health. C/EBP homologous protein (CHOP) is induced by ER stress and has a central role in apoptotic execution pathways triggered by ER stress. The aim of this study was to characterise the role of CHOP in obesity and insulin resistance. METHODS: Metabolic studies were performed in Chop ( -/- ) and wild-type C57Bl/6 mice, and included euglycaemic-hyperinsulinaemic clamps and indirect calorimetry. The inflammatory state of liver and adipose tissue was determined by quantitative RT-PCR, immunohistology and macrophage cultures. Viability and absence of ER stress in islets of Langerhans was determined by electron microscopy, islet culture and quantitative RT-PCR. RESULTS: Systemic deletion of Chop induced abdominal obesity and hepatic steatosis. Despite marked obesity, Chop ( -/- ) mice had preserved normal glucose tolerance and insulin sensitivity. This discrepancy was accompanied by lower levels of pro-inflammatory cytokines and less infiltration of immune cells into fat and liver. CONCLUSIONS/INTERPRETATION: These observations suggest that insulin resistance is not induced by fat accumulation per se, but rather by the inflammation induced by ectopic fat. CHOP may play a key role in the crosstalk between excessive fat deposition and induction of inflammation-mediated insulin resistance.
Type de document :
Article dans une revue
Diabetologia, Springer Verlag, 2012, 55 (4), pp.1167-78. 〈10.1007/s00125-011-2427-7〉
Liste complète des métadonnées
http://www.hal.inserm.fr/inserm-00817778
Contributeur : Marie Francoise Simon <>
Soumis le : jeudi 25 avril 2013 - 12:03:28
Dernière modification le : jeudi 4 octobre 2018 - 09:50:09

Lien texte intégral

openaccess

Identifiants

Collections

UNIV-TLSE3

Citation

M. Maris, L. Overbergh, C. Gysemans, A. Waget, A. K. Cardozo, et al.. Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance.. Diabetologia, Springer Verlag, 2012, 55 (4), pp.1167-78. 〈10.1007/s00125-011-2427-7〉. 〈inserm-00817778〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

53

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD