Xue Ying, Xu Cheng, Lv Mengqing, Li JiaHui, Wen Kang, Geng Tuoyu, Gong Daoqing, Liu Long, Fallahshahroudi Amir, Zheng Yun
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China.
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China.
Poult Sci. 2025 Jul;104(7):105219. doi: 10.1016/j.psj.2025.105219. Epub 2025 Apr 25.
Goose fatty liver, a product of short-term overfeeding, is notable for its high nutritional value and unique tolerance to severe steatosis without inflammation, in contrast to human nonalcoholic fatty liver disease (NAFLD). It is known that choline can alleviate nonalcoholic steatohepatitis and liver cirrhosis, inhibit cell apoptosis, promote lecithin synthesis and fat transportation out of the liver, and relieve cardiovascular disease-related symptoms (e.g., hyperlipidemia and hypercholesterolemia). This study investigates the role of Proline Rich Membrane Anchor 1 (PRIMA1) in inhibiting inflammation through choline metabolism during goose fatty liver formation. Overfeeding of geese resulted in increased body and liver weights, elevated fat content, and significantly higher expression of PRIMA1, accompanied by decreased LITAF and CRP (important pro-inflammatory cytokines) expression and reduced acetylcholinesterase (AchE) activity, which was assessed by the amount of produced choline. The overexpression of PRIMA1 in goose primary hepatocytes (GPHs) enhanced AchE activity. Consistently, glucose-induced upregulation of PRIMA1 expression in GPHs was accompanied by increased AchE activity. Further combined treatment with glucose and PRIMA1 knockdown in GPHs showed that downregulation of PRIMA1 attenuated the suppression of LITAF and CRP expression caused by glucose addition, but had no effect on the rise in AchE activity. These findings indicate that PRIMA1 may play a role in promoting choline metabolism and protecting against liver inflammation, offering insights into potential therapeutic targets for NAFLD.
鹅脂肪肝是短期过度喂养的产物，与人类非酒精性脂肪性肝病（NAFLD）不同，它以高营养价值和对严重脂肪变性而无炎症的独特耐受性而著称。已知胆碱可缓解非酒精性脂肪性肝炎和肝硬化，抑制细胞凋亡，促进卵磷脂合成以及脂肪从肝脏转运出去，并缓解心血管疾病相关症状（如高脂血症和高胆固醇血症）。本研究调查富含脯氨酸的膜锚定蛋白1（PRIMA1）在鹅脂肪肝形成过程中通过胆碱代谢抑制炎症的作用。对鹅过度喂养导致体重和肝脏重量增加、脂肪含量升高，PRIMA1表达显著上调，同时脂多糖诱导肿瘤坏死因子α（LITAF）和C反应蛋白（CRP）（重要的促炎细胞因子）表达降低以及乙酰胆碱酯酶（AchE）活性降低，后者通过所产生的胆碱量来评估。在鹅原代肝细胞（GPHs）中PRIMA1的过表达增强了AchE活性。同样，葡萄糖诱导的GPHs中PRIMA1表达上调伴随着AchE活性增加。在GPHs中进一步将葡萄糖与PRIMA1敲低联合处理表明，PRIMA1的下调减弱了葡萄糖添加所引起的LITAF和CRP表达的抑制，但对AchE活性的升高没有影响。这些发现表明PRIMA1可能在促进胆碱代谢和预防肝脏炎症中发挥作用，为NAFLD的潜在治疗靶点提供了见解。
