Department of Nutrition, Health Sciences School, Ariel University, Israel.
Department of Nutrition, Health Sciences School, Ariel University, Israel
Biosci Rep. 2019 May 14;39(5). doi: 10.1042/BSR20190054. Print 2019 May 31.
Dietary fat overload (typical to obesity) increases the risk of pancreatic pathologies through mechanisms yet to be defined. We previously showed that saturated dietary fat induces pancreatic acinar lipotoxicity and cellular stress. The endoplasmic reticulum (ER) of exocrine pancreas cells is highly developed and thus predisposed to stress. We studied the combination of saturated and unsaturated FAs in metabolic and pancreatitis like cerulein (CER)-induced stress states on cellular ER stress.Exocrine pancreas AR42J and rat primary exocrine acinar cells underwent acute (24 h) challenge with different FAs (saturated, monounsaturated) at different concentrations (250 and 500 µM) and in combination with acute CER-induced stress, and were analyzed for fat accumulation, ER stress unfolded protein response (UPR) and immune and enzyme markers. Acute exposure of AR42J and pancreatic acinar cells to different FAs and their combinations increased triglyceride accumulation. Palmitic acid significantly dose-dependently enhanced the UPR, immune factors and pancreatic lipase (PL) levels, as demonstrated by XBP1 splicing and elevation in UPR transcripts and protein levels ( and ). Exposure to high palmitic levels in a CER-induced stress state synergistically increased ER stress and inflammation marker levels. Exposure to oleic acid did not induce ER stress and PL levels and significantly decreased immune factors in an acute CER-induced stress state. Combination of oleic and palmitic acids significantly reduced the palmitic-induced ER stress, but did not affect the immune factor response. We show that combination of monounsaturated and saturated FAs protects from exocrine pancreatic cellular ER stress in both metabolic and CER-induced stress.
饮食脂肪过量（肥胖的典型特征）会通过尚未明确的机制增加患胰腺疾病的风险。我们之前的研究表明，饱和膳食脂肪会诱导胰腺腺泡细胞的脂肪毒性和细胞应激。外分泌胰腺细胞的内质网（ER）高度发达，因此容易受到应激。我们研究了在代谢和类似 cerulein（CER）诱导的应激状态下，饱和和不饱和 FA 的组合对细胞 ER 应激的影响。外分泌胰腺 AR42J 和大鼠原代外分泌腺泡细胞在急性（24 小时）用不同浓度（250 和 500 µM）的不同 FA（饱和、单不饱和）和急性 CER 诱导的应激下进行了急性挑战，并对脂肪积累、ER 应激未折叠蛋白反应（UPR）和免疫及酶标记物进行了分析。AR42J 和胰腺腺泡细胞急性暴露于不同的 FA 及其组合会增加甘油三酯的积累。棕榈酸显著地剂量依赖性地增强了 UPR、免疫因子和胰脂肪酶（PL）水平，这表现为 XBP1 剪接和 UPR 转录物和蛋白水平的升高（和）。在 CER 诱导的应激状态下，高棕榈酸水平的暴露协同地增加了 ER 应激和炎症标志物水平。在急性 CER 诱导的应激状态下，油酸暴露不会诱导 ER 应激和 PL 水平，并显著降低免疫因子水平。油酸和棕榈酸的组合显著降低了棕榈酸诱导的 ER 应激，但对免疫因子反应没有影响。我们表明，在代谢和 CER 诱导的应激中，单不饱和和饱和 FA 的组合可保护外分泌胰腺细胞的 ER 应激。
