Rius-Pérez Sergio, Torres-Cuevas Isabel, Monsalve María, Miranda Francisco J, Pérez Salvador
Department of Physiology, Faculty of Pharmacy, University of Valencia, Avda. Vicente Andres Estelles s/n, 46100 Burjassot, Spain.
Neonatal Research Group, Health Research Institute La Fe, 46026 Valencia, Spain.
Antioxidants (Basel). 2020 Sep 19;9(9):887. doi: 10.3390/antiox9090887.
Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1α in inflammatory response regulation in the liver and its contribution to the detrimental effect of obesity on the liver during acute pancreatitis. For this purpose, we induced acute pancreatitis by cerulein in not only wild-type (WT) and PGC-1α knockout (KO) mice, but also in lean and obese mice. PGC-1α levels were up-regulated in the mice livers with pancreatitis. The increased PGC-1α levels were bound to p65 to restrain its transcriptional activity toward . Lack of PGC-1α favored the assembly of the p65/phospho-STAT3 complex, which promoted expression during acute pancreatitis. The increased transcript levels and the pro-oxidant liver status caused by the down-regulated expression of the PGC-1α-dependent antioxidant genes enhanced nitrosative stress and decreased energy charge in the livers of the PGC-1α KO mice with pancreatitis. It is noteworthy that the PGC-1α levels lowered in the obese mice livers, which increased the mRNA expression and protein nitration levels and decreased energy charge during pancreatitis. In conclusion, obesity impairs PGC-1α up-regulation in the liver to cause nitrosative stress during acute pancreatitis.
急性胰腺炎是胰腺组织的一种炎症过程，常导致远处器官功能障碍。虽然肝损伤在急性胰腺炎中并不常见，但肥胖是发生肝脏并发症的一个危险因素。这项研究的目的是评估PGC-1α在肝脏炎症反应调节中的作用及其对肥胖在急性胰腺炎期间对肝脏有害影响的作用。为此，我们不仅在野生型（WT）和PGC-1α基因敲除（KO）小鼠中，而且在瘦小鼠和肥胖小鼠中用雨蛙肽诱导急性胰腺炎。胰腺炎小鼠肝脏中PGC-1α水平上调。升高的PGC-1α水平与p65结合，以抑制其对……的转录活性。缺乏PGC-1α有利于p65/磷酸化STAT3复合物的组装，该复合物在急性胰腺炎期间促进……表达。PGC-1α依赖性抗氧化基因表达下调导致的转录……水平升高和肝脏促氧化状态增强了胰腺炎PGC-1α基因敲除小鼠肝脏中的亚硝化应激并降低了能量电荷。值得注意的是，肥胖小鼠肝脏中的PGC-1α水平降低，这增加了……mRNA表达和蛋白质硝化水平，并在胰腺炎期间降低了能量电荷。总之，肥胖会损害肝脏中PGC-1α的上调，从而在急性胰腺炎期间引起亚硝化应激。
