title: Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver.
abstract: 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 (30mg/kg/day), metformin (300mg/kg/day), metformin (150mg/kg/day), metformin (300mg/kg/day) with celecoxib (30mg/kg/day), and metformin (150mg/kg/day) with celecoxib (15mg/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-α, 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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center (NDMC), Taipei, Taiwan; Department of Medical Research, NDMC, Taipei, Taiwan.
authors.forename: Chieh-Hua
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center (NDMC), Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Hung
authors.affiliation: Department of Medical Research, NDMC, Taipei, Taiwan; Department of Physiology and Biophysics, NDMC, Taipei, Taiwan; Institute of Preventive Medicine, NDMC, Taipei, Taiwan. Electronic address: pshsieh@hotmail.com.
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000068579:Celecoxib / Q000494:pharmacology* / Q000627:therapeutic use; D048429:Cell Size / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009765:Obesity / Q000139:chemically induced / Q000150:complications; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; D052246:Cyclooxygenase 2 Inhibitors; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D000068579:Celecoxib
keywords: Adipose tissue inflammation; COX-2 inhibitor; Fatty liver; Insulin resistance; Metformin; Obesity