Obesity-induced pancreatopathy in rats is reversible after bariatric surgery

Abstract

Obesity is a risk factor for pancreatic diseases. Bariatric surgery is one of the most efficient treatments of morbid obesity. The aims were to assess pancreatic endocrine and exocrine lesions in obese rats, to analyze effects of bariatric surgery. Sixty-three male Wistar rats were included in five groups: 2 fed with high fat diet (HFD) or normal diet for 3 months, 2 fed with HFD or normal diet for 6 months; 1 group fed with HFD and undergoing bariatric surgery (n = 30). Quantitative MR imaging was performed in HFD6, ND6 and HFD3-BS. Pancreas specimens were analyzed after sacrifice for adipocyte infiltration, fibrosis, acinar-ductal metaplasia, abnormality of Langerhans islets (HHF: hypertrophy, hypervascularisation, fibrosis), and hemosiderin deposits in acinar or endocrine locations. We found that HFD6 rats had more fibro-inflammatory islets (P = 0.0139) and acinar-ducal metaplasia (P = 0.0843) than HFD3 rats. Rats with HFD3+6 had more fibro-inflammatory islets (P < 0.0001), hemosiderin deposits (p < 0.0001), fat infiltration (P = 0.0008) and acinar-ductal metaplasia lesions (P = 0.0424). Weight increase was associated with glycoregulation abnormalities (r = 0.44, P = 0.08) and adipocyte infiltrations (P = 0.009). After surgery, less fibro-inflammatory islets (P = 0.0004), fat and iron infiltrates (P = 0.005 and P = 0.06), and acino-ductal metaplasia (P = 0.05) were observed compared to HFD6 rats. MR image quantifications revealed increased elasticity, fat fraction, and R2 and a decreased elasticity wave dispersion coefficient in the high fat groups that reversed after surgery. MRI parameters were in strong correlation with respective histological counterparts. In conclusion, obese rats develop pancreatic inflammatory lesions with acinar-ductal metaplasia in acinar location and the endocrine-exocrine interface. These changes can be prevented by bariatric surgery. Quantitative MR imaging is accurate in identifying early pancreatic lesions.