Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, prevents pancreatic degeneration in obese and diabetic rats

Damage to the exocrine pancreas has been observed in patients and animals with hyperlipidemia and hyperglycemia. Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, has been shown to improve lipid and glucose metabolism, and to interfere with the inflammatory response.To examine the effects of bezafibrate on exocrine pancreas in hyperlipidemic obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have no cholecystokinin-1 receptor gene expression.One group of rats (n = 8) received a bezafibrate-rich diet (150 mg/100 g normal chow) from 12 weeks of age until 30 weeks of age, whereas a control group (n = 8) received standard rat chow.Bezafibrate treatment significantly reduced serum triglyceride, total cholesterol, and free fatty acids levels and significantly increased the pancreatic wet weight (1,145 +/- 54 vs 874 +/- 33 mg/rat, p0.01), and protein (169 +/- 7 vs 128 +/- 11 mg/pancreas p0.01) and enzyme contents in the pancreas compared with those in untreated control rats. Immunohistochemical studies of the pancreas showed that expression of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, and alpha-smooth muscle actin in bezafibrate-treated rats was greatly suppressed compared with that in the untreated control rats. The histopathologic changes such as vacuolar degeneration and tubular complexes observed in the control rat pancreas were markedly improved in bezafibrate-treated rats.Our results suggest that bezafibrate reduces hyperlipidemia, inhibits pancreatic inflammation, and prevents pancreatic degeneration in obese and diabetic OLETF rats.