%0 Journal Article %T Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance. %+ Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven (LEGENDO) %+ Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) %+ Université libre de Bruxelles (ULB) %+ Department of School Health, Faculty of Education & Department of Molecular Genetics, Kumamoto University, Kumamoto %A Maris, M. %A Overbergh, L. %A Gysemans, C. %A Waget, A. %A Cardozo, A. K. %A Verdrengh, E. %A Cunha, J. P. M. %A Gotoh, T. %A Cnop, M. %A Eizirik, D. L. %A Burcelin, R. %A Mathieu, C. %< avec comité de lecture %@ 0012-186X %J Diabetologia %I Springer Verlag %V 55 %N 4 %P 1167-78 %8 2012-04 %D 2012 %R 10.1007/s00125-011-2427-7 %M 22237685Journal articles %X 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. %G English %L inserm-00817778 %U https://inserm.hal.science/inserm-00817778 %~ INSERM %~ UNIV-TLSE3 %~ UNIV-UT3 %~ UT3-INP %~ UT3-TOULOUSEINP %~ I2MC