OBJECTIVES: 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.
OBJECTIVES: 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 obesepatients.
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Authors: Maria Pini; Davina H Rhodes; Karla J Castellanos; Robert J Cabay; Eileen F Grady; Giamila Fantuzzi Journal: PLoS One Date: 2012-07-16 Impact factor: 3.240