| Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice. | |
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MedLine Citation:
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PMID: 21386801 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Objective:Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice.Design:Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age.Results:Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice.Conclusion:The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.International Journal of Obesity advance online publication, 8 March 2011; doi:10.1038/ijo.2011.55. |
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Authors:
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K S Bell-Anderson; L Aouad; H Williams; F R Sanz; J Phuyal; C Z Larter; G C Farrell; I D Caterson |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-08 |
Journal Detail:
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Title: International journal of obesity (2005) Volume: - ISSN: 1476-5497 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256108 Medline TA: Int J Obes (Lond) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] School of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia [2] Boden Institute of Obesity, Nutrition & Exercise, University of Sydney, Sydney, New South Wales, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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