Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 789, Issue -, Pages 60-67Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2016.07.012
Keywords
Metformin; COX-2 inhibitor; Obesity; Adipose tissue inflammation; Insulin resistance; Fatty liver
Categories
Funding
- National Science Council of the R.O.C. [NSC 101-2320-B-016-001-MY3]
- Tri-Service General Hospital [TSGH-C103-007-S01, TSGH-C103-127]
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We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats. Male Sprague-Dawley rats were fed with either regular or HF diet for 8 weeks. Rats fed with regular diet were treated with vehicle for further 4 weeks. HF fed rats were divided into 6 groups, namely, vehicle, celecoxib (30 mg/kg/ day), metformin (300 mg/kg/day), metformin (150 mg/kg/day), metformin (300 mg/kg/day) with celecoxib (30 mg/kg/day), and metformin (150 mg/kg/day) with celecoxib (15 mg/kg/day) for additional 4 weeks. Increased body weight in HF fed rats was significantly reduced by metformin alone and metformin combined with celecoxib. The increases in the HOMA-IR value and the area under the curve of glucose following an oral glucose tolerance test, systolic blood pressure, and adipocyte size were significantly diminished in treated rats, especially rats undergoing combined treatment. Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-alpha, MCP-1, and leptin levels in high-fat (HF) fed rats. Furthermore, the elevated hepatic triglycerides content was significantly decreased in the combined treatment group compared to that of groups of celecoxib or metformin alone. Celecoxib exerts a synergistic beneficial effect with metformin on and obesity-associated metabolic and cardiovascular disorders in high-fat fed rats. (C) 2016 Elsevier B.V. All rights reserved.
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