Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Life Sci. 2023 Jun 1;322:121670. doi: 10.1016/j.lfs.2023.121670. Epub 2023 Apr 6.
Dysregulation of pancreatic fat and lipotoxic inflammation are common clinical findings in alcoholic chronic pancreatitis (ACP). In this study, we investigated a relationship between dysregulated pancreatic lipid metabolism and the development of injury in a chronic ethanol (EtOH) feeding model of hepatic alcohol dehydrogenase 1- deficient (ADH) deer mice.
ADH and hepatic ADH normal (ADH) deer mice were fed a liquid diet containing 3 % EtOH for three months and received a single gavage of binge EtOH with/without fatty acid ethyl esters (FAEEs) one week before the euthanasia. Plasma and pancreatic tissue were analyzed for lipids including FAEEs, inflammatory markers and adipokines using GC-MS, bioassays/kits, and immunostaining, respectively. Pancreatic morphology and proteins involved in lipogenesis were determined by the H & E staining, electron microscopy and Western blot analysis.
Chronic EtOH feeding in ADH vs. ADH deer mice resulted in a significant increase in the levels of pancreatic lipids including FAEEs, adipokines (leptin and resistin), fat infiltration with inflammatory cells and lipid droplet deposition along with the proteins involved in lipogenesis. The changes exacerbated by an administration of binge EtOH with/without FAEEs in the pancreas of ADH vs. ADH deer mice fed chronic EtOH suggest a metabolic basis for ACP.
These findings suggest that the liver-pancreatic axis plays a crucial role in etiopathogenesis of ACP, as the increased body burden of EtOH due to hepatic ADH deficiency exacerbates pancreatic injury.
胰腺脂肪和脂肪毒性炎症失调是酒精性慢性胰腺炎（ACP）的常见临床发现。在这项研究中，我们研究了肝乙醇脱氢酶 1 缺乏（ADH）鹿鼠慢性乙醇（EtOH）喂养模型中胰腺脂质代谢失调与损伤发展之间的关系。
ADH 和肝 ADH 正常（ADH）鹿鼠接受含有 3%EtOH 的液体饮食喂养三个月，并在安乐死前一周接受一次 binge EtOH 加/不加脂肪酸乙酯（FAEE）灌胃。使用 GC-MS、生物测定/试剂盒和免疫染色分别分析血浆和胰腺组织中的脂质，包括 FAEE、炎症标志物和脂肪因子。通过 H&E 染色、电子显微镜和 Western blot 分析确定胰腺形态和参与脂肪生成的蛋白质。
与 ADH 鹿鼠相比，慢性 EtOH 喂养在 ADH 鹿鼠中导致胰腺脂质水平显著增加，包括 FAEE、脂肪因子（瘦素和抵抗素）、脂肪浸润伴炎症细胞和脂滴沉积，以及参与脂肪生成的蛋白质。在慢性 EtOH 喂养的 ADH 鹿鼠中给予 binge EtOH 加/不加 FAEE 后，这些变化加剧，提示 ACP 的代谢基础。
这些发现表明肝-胰腺轴在 ACP 的发病机制中起着至关重要的作用，因为由于肝 ADH 缺乏导致的乙醇体负荷增加会加剧胰腺损伤。
