Rosiglitazone aggravates nonalcoholic Fatty pancreatic disease in C57BL/6 mice fed high-fat and high-sucrose diet.
OBJECTIVE
Evaluate the effect of fenofibrate, bezafibrate, and rosiglitazone on nonalcoholic fatty pancreatic disease and islet peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-beta immunostain in mice fed high-fat high-sucrose (HFHS) diet.


METHODS
Two-month-old male mice were fed standard chow (n = 10) or HFHS chow (n = 40) for 6 weeks. Afterward, HFHS mice were grouped by treatment: untreated HFHS and HFHS treated with rosiglitazone (HFHS-Ro), fenofibrate (HFHS-Fe), or bezafibrate (HFHS-Bz). Medications were administered for 5 weeks. After treatment, the pancreas was removed and analyzed by morphometry, stereology, and immunohistochemistry.


RESULTS
The HFHS-fed mice showed altered fasting glucose (+33%) and insulin (+138%); increased body (+20%) and pancreas (+28%) masses, pancreatic fat (+700%), islet hypertrophy (+38%); and decreased GLUT2 immunostain (-60%). Rosiglitazone reduced fasting glucose and insulin but induced weight gain. Fibrates impeded weight gain, but only bezafibrate prevented islet hypertrophy. The GLUT2 stain was improved in all treatments, and there were no alterations in PPAR-alpha. There were morphological signs of pancreatitis with fenofibrate, although there were no alterations in amylase and lipase. Rosiglitazone exacerbated pancreatic fat infiltration (+75% vs HFHS group), and bezafibrate increased PPAR-beta expression in pancreatic islets.


CONCLUSIONS
Rosiglitazone is shown for the first time to exacerbate pancreatic fat infiltration; therefore, precaution has to be taken when rosiglitazone is prescribed to obese patients.
Fernandes-Santos
Caroline
C
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Evangelista Carneiro
Rafael
R
de Souza Mendonca
Leonardo
L
Barbosa Aguila
Márcia
M
Mandarim-de-Lacerda
Carlos Alberto
CA
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004041:Dietary Fats / Q000494:pharmacology*; D019422:Dietary Sucrose / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000633:toxicity*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy; D047493:PPAR alpha / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D004041:Dietary Fats; D019422:Dietary Sucrose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D047493:PPAR alpha; D048068:PPAR-beta; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate; D001629:Bezafibrate