| Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance. | |
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MedLine Citation:
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PMID: 22237685 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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M Maris; L Overbergh; C Gysemans; A Waget; A K Cardozo; E Verdrengh; J P M Cunha; T Gotoh; M Cnop; D L Eizirik; R Burcelin; C Mathieu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
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Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Herestraat 49 bus 902, 3000, Leuven, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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