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| Nonalcoholic fatty liver disease aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice |
| Tian-Yu Lin a , b , Yi-Fan Zhang a , b , Yang Wang a , b , Yun Liu a , b , Jun Xu c , Yu-Lan Liu a , b , ∗ |
a Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
b Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
c Central Laboratory & Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
∗Corresponding author at: Department of Gastroenterology, Peking University People’s Hospital, No. 11 South Street, Xizhimen, Beijing 100044, China
E-mail address: liuyulan@pkuph.edu.cn (Y.-L. Liu). |
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Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for severe acute pancreatitis (AP). The underlying mechanism remains unclear. We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.
Methods: C57BL/6N mice were fed on a high-fat diet (HFD) to generate the NAFLD model, and mice in the control group were provided with a normal diet (ND). After being anesthetized with ketamine/xylazine, mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP, and sham operation (SO) was used as control. Serum amylase and Schmidt’s pathological score system were used to evaluate AP severity. Bacterial loads, total cholesterol level, and cholesterol metabolic-associated molecules [low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1)] were analyzed in the liver and pancreas.
Results: Compared with the ND-AP group, mice in the HFD-AP group had severer pancreatitis, mani- fested with higher serum amylase levels and higher AP pathologic scores, especially the inflammation and hemorrhage scores. Compared with the HFD-SO group and ND-AP group, bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group. Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas, although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.
Conclusions: NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.
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2023, Vol. 22 
