Impact of intermittent fasting versus vitamin D on high fat fructose-induced pancreatic steatosis: possible role of aquaporins.

BACKGROUND: The molecular basis of pancreatic steatosis is not entirely known. Aquaporins (AQPs) are integral membrane proteins involved in a variety of pancreatic functions. Given the little data regarding the potential role of aquaporins in the pathogenesis of pancreatic steatosis, this study was designed to assess the role of aquaporins and the NLRP3-inflammasome in the rat model of high-fat fructose diet (HFFD) and to investigate the impact of vitamin D supplementation and alternate day fasting (ADF) in ameliorating HFFD-induced pancreatic steatosis. METHOD: Twenty-four Sprague-Dawley male rats were divided equally into 4 groups. Group I (control group), Group II (HFFD group), Group III (HFFD + ADF group), and Group IV (HFFD + vitamin D group). By the end of the experiment, fasting blood samples were collected for determination of blood glucose, serum insulin, lipid profile, and insulin resistance. Oxidative stress biomarkers (malondialdehyde and reduced glutathione), inflammatory markers (interleukin-1β and TNF-α), and expression of aquaporins (AQP-1, AQP-3, and AQP-7) genes were evaluated in pancreatic tissues. Histopathological examination of the pancreas and immunohistochemistry of the NLRP3-infammasome and AQP-7 were performed. RESULTS: The HFFD group exhibited pancreatic steatosis with a significant elevation in the levels of blood sugar, serum insulin, insulin resistance, lipid profile, oxidative stress, inflammatory markers, and AQP-3 and AQP-7 mRNA expressions. Regarding histopathology, there were pale vacuolated-stained cytoplasm in acinar pancreatic cells and increased immunoreactivity for AQP-7 and NLRP3-inflammasome. All these parameters improved with ADF and vitamin D supplementation, with more favorable effects for ADF. CONCLUSION: ADF and vitamin D treatment ameliorated the effect of the high-fat fructose diet at both levels of the biochemical and histopathological examinations.