Rofecoxib impairs adipose tissue development in a murine model of nutritionally induced obesity

H. Roger Lijnen; Berthe Van Hoef; Hua Rong Lu; David J. Gallacher

doi:10.1160/TH08-02-0114

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(02): 338-342
DOI: 10.1160/TH08-02-0114

Animal Models

Schattauer GmbH

Rofecoxib impairs adipose tissue development in a murine model of nutritionally induced obesity

H. Roger Lijnen

¹Center for Molecular andVa scular Biology, KU Leuven, Leuven, Belgium

,

Berthe Van Hoef

¹Center for Molecular andVa scular Biology, KU Leuven, Leuven, Belgium

,

Hua Rong Lu

²Center of Excellence for Cardiovascular Safety Research, Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium

,

David J. Gallacher

²Center of Excellence for Cardiovascular Safety Research, Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium

› Author Affiliations

Abstract

Summary

The effect of rofecoxib (Vioxx), a cyclooxygenase (COX)-2 inhibitor, on adipose tissue development was studied in a murine model of diet-induced obesity. Oral administration of Vioxx for six weeks (34 mg/kg/day) to C57Bl/6 mice kept on high-fat diet (n = 19) resulted in a significant reduction in total body weight (p < 0.01) and of subcutaneous (p < 0.05) and gonadal (p< 0.01) adipose tissue mass, as compared to placebo-treated animals (n = 21).There was no significant difference in food intake between both groups (2.8 ± 0.09 vs.3.0 ± 0.10 g/day;p = 0.20).Administration ofVioxx resulted in reduced total cholesterol and high-density lipoprotein (HDL) cholesterol levels (p < 0.0001) and in enhanced levels of liver enzymes, as compared to placebo. In the gonadal but not in the subcutaneous adipose tissue, adipocytes were smaller after Vioxx treatment (p < 0.05).The macrophage content was significantly lower in gonadal adipose tissues of Vioxx-treated mice (p < 0.05), but not in the subcutaneous adipose tissues. This was, however, not associated with differences in adipose tissue levels of the pro-inflammatory tumor necrosis factor (TNF)-α. Blood vessel size or density in either fat pad were not affected by Vioxx treatment. Thus, in a nutritionally induced murine obesity model, oral administration of Vioxx, as compared to placebo, resulted in reduced adipose tissue development, associated with lower feeding efficiency and smaller adipocytes.

Keywords

Obesity - adipose tissue - cyclooxygenase - rofecoxib

Full Text

References

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