Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice

Adiponectin is recognized as an antiinflammatory and antifibrotic protein derived from adipocytes, and low serum adiponectin levels are present in obesity. Recent studies have highlighted the relationship between obesity and pancreatic diseases. However, the role of adiponectin in chronic pancreatitis remains uncertain. The aim of this study was to determine the effects of adiponectin in chronic pancreatitis. We investigated the effects of adiponectin in experimental chronic pancreatitis by using adiponectin-knockout (APN-KO) mice. Chronic pancreatitis was induced by repeated hourly (6 times) intraperitoneal injections of 50 A mu g/kg cerulein three times per week for 4 weeks in wild-type (WT) and APN-KO mice. We evaluated the severity of chronic pancreatitis biochemically and morphologically. In cerulein-treated mice, macroscopically and histologically, severe pancreatic damage was observed in APN-KO mice compared with findings in WT mice. The histological scores for chronic pancreatitis, including glandular atrophy, pseudotubular complex, fibrosis, and total scores, were significantly higher in APN-KO mice than in WT mice. Activated pancreatic stellate cells and F4/80-positive pancreatic macrophages accumulated in the pancreas of APN-KO mice but not in WT mice. Overexpression of the mRNAs of transforming growth factor-beta 1, CD68, and monocyte chemoattractant protein-1 was noted in APN-KO mice but not in WT mice. The gene expression level of collagen1 (alpha 1) tended to be higher in APN-KO mice than in WT mice, albeit insignificantly. Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice. Hypoadiponectinemia could enhance the severity of chronic pancreatitis.