Suppressive effect of COX2 inhibitor on the progression of adipose inflammation in high-fat-induced obese rats.
BACKGROUND
The aim was to examine whether the inhibition of selective cyclooxygenase (COX) 2 activation could suppress the development of inflammatory reaction in visceral and subcutaneous abdominal fats of high-fat-induced obese rats.


METHODS
The rats were fed separately regular diet (CONT), high-fat diet ad libitum or energy-restrictedly (HFr) for 12 weeks. Rats fed high-fat diet ad libitum were further divided into those co-treated with vehicle (HFa), a selective COX2 inhibitor-celecoxib (HFa-Cel) or nimesulide (HFa-Nim). Oral glucose tolerance test (OGTT) was performed at the end of weeks 4, 8, 12. Another set of rats with similar grouping was divided into those with a 4-, 8- or 12-week intervention for tissue sampling.


RESULTS
Body and epididymal fat weights were increased similarly in HFa, HFa-Cel and HFa-Nim. Time-dependent increases in plasma insulin, triglyceride, impaired OGTT shown in HFa were significantly reversed in HFa-Cel and HFa-Nim. The obese-linked increases in gene expressions of COX-2, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha) in epididymal and subcutaneous fats (especially in the former) were significantly suppressed in HFa-Cel and HFa-Nim. The protein contents of MCP-1 and TNF-alpha in epididymal fats were changed consistently with their gene expressions. Plasma MCP-1 was increased time-dependently in HFa and suppressed in HFa-Cel and HFa-Nim. The increased CD68 positive cells showed in both epididymal and subcutaneous fats of HFa were significantly attenuated in HFa-Cel and HFa-Nim.


CONCLUSIONS
Our findings suggest that COX2 activation is crucially involved in the development of inflammatory response in adipose tissues of high-fat-induced obese rats.
Hsieh
P-S
PS
National Defense Medical Center, Taipei, Taiwan. pshsieh@hotmail.com
Lu
K-C
KC
Chiang
C-F
CF
Chen
C-H
CH
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D000068579:Celecoxib; D018932:Chemokine CCL2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005223:Fats / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000032:analysis; D050152:Intra-Abdominal Fat / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050507:Subcutaneous Fat, Abdominal / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D000068579:Celecoxib; D018932:Chemokine CCL2; D052246:Cyclooxygenase 2 Inhibitors; D005223:Fats; D007328:Insulin; D011720:Pyrazoles; D013449:Sulfonamides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C111835:CCL2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C012655:nimesulide