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alpha-Tocopherol supplementation reduces inflammation and apoptosis in high cholesterol mediated nonalcoholic steatohepatitis
Biofactors ( IF 6 ) Pub Date : 2021-06-08 , DOI: 10.1002/biof.1700
Tugce Demirel-Yalciner 1 , Erdi Sozen 1 , Esra Ozaltin 1 , Ali Sahin 1 , Nesrin Kartal Ozer 1
Affiliation  

Inflammation and apoptosis signaling are crucial steps in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Alpha-tocopherol, the most active form of vitamin E, is an important modulator of signaling mechanisms, but its involvement to cholesterol-induced NASH pathogenesis remains poorly defined. Herein we have reported a novel effect of α-tocopherol in the transition from hepatic steatosis to NASH. High cholesterol diet alone (without α-tocopherol) in rabbits elevated NASH development as indicated by increased inflammatory response, apoptotic activity and liver fibrosis. Such elevation results from induction of signaling mechanisms since the expressions of IL1β, phospho c-Jun/c-Jun ratio, JNK, caspase 9, CHOP and Bax were increased, and recruitment of macrophage, α-smooth muscle actin (α-SMA) and COL1A1 into the liver tissue were induced. Alpha-tocopherol supplementation inhibited inflammatory response, apoptosis and fibrosis development without affecting lipid accumulation in high cholesterol-induced NASH. Specifically, α-tocopherol lowered the inflammatory level as observed by reduced macrophage infiltration and JNK/c-Jun signaling. Lower inflammatory status co-occurred with the reduction of CHOP and Bax expressions as well as fibrosis-related COL1A1 and α-SMA levels. Taken together, α-tocopherol supplementation inhibits cholesterol-induced NASH development by lowering JNK/c-Jun/inflammation axis in addition to JNK/CHOP/apoptosis signaling, which might contribute to resistance against NAFLD/NASH transition.

中文翻译:

α-生育酚补充剂可减少高胆固醇介导的非酒精性脂肪性肝炎的炎症和细胞凋亡

炎症和细胞凋亡信号传导是从非酒精性脂肪性肝病 (NAFLD) 到非酒精性脂肪性肝炎 (NASH) 的关键步骤。α-生育酚是维生素 E 最活跃的形式,是信号机制的重要调节剂,但其与胆固醇诱导的 NASH 发病机制的关系仍不清楚。在此,我们报道了 α-生育酚在从肝脂肪变性向 NASH 转变中的新作用。兔子单独的高胆固醇饮食(不含 α-生育酚)会增加 NASH 的发展,这表现为炎症反应、细胞凋亡活动和肝纤维化增加。这种升高是由于 IL1β、磷酸化 c-Jun/c-Jun 比率、JNK、半胱天冬酶 9、CHOP 和 Bax 的表达增加以及巨噬细胞募集、α-平滑肌肌动蛋白 (α-SMA) 和 COL1A1 被诱导进入肝组织。α-生育酚补充剂可抑制炎症反应、细胞凋亡和纤维化发展,而不会影响高胆固醇诱导的 NASH 中的脂质积累。具体而言,α-生育酚降低了炎症水平,如通过减少巨噬细胞浸润和 JNK/c-Jun 信号传导所观察到的。较低的炎症状态与 CHOP 和 Bax 表达以及纤维化相关的 COL1A1 和 α-SMA 水平的降低同时发生。总之,除了 JNK/CHOP/细胞凋亡信号之外,α-生育酚补充剂还通过降低 JNK/c-Jun/炎症轴来抑制胆固醇诱导的 NASH 发展,这可能有助于抵抗 NAFLD/NASH 转变。α-生育酚补充剂可抑制炎症反应、细胞凋亡和纤维化发展,而不会影响高胆固醇诱导的 NASH 中的脂质积累。具体而言,α-生育酚降低了炎症水平,如通过减少巨噬细胞浸润和 JNK/c-Jun 信号传导所观察到的。较低的炎症状态与 CHOP 和 Bax 表达以及纤维化相关的 COL1A1 和 α-SMA 水平的降低同时发生。总之,除了 JNK/CHOP/细胞凋亡信号之外,α-生育酚补充剂还通过降低 JNK/c-Jun/炎症轴来抑制胆固醇诱导的 NASH 发展,这可能有助于抵抗 NAFLD/NASH 转变。α-生育酚补充剂可抑制炎症反应、细胞凋亡和纤维化发展,而不会影响高胆固醇诱导的 NASH 中的脂质积累。具体而言,α-生育酚降低了炎症水平,如通过减少巨噬细胞浸润和 JNK/c-Jun 信号传导所观察到的。较低的炎症状态与 CHOP 和 Bax 表达以及纤维化相关的 COL1A1 和 α-SMA 水平的降低同时发生。总之,除了 JNK/CHOP/细胞凋亡信号之外,α-生育酚补充剂还通过降低 JNK/c-Jun/炎症轴来抑制胆固醇诱导的 NASH 发展,这可能有助于抵抗 NAFLD/NASH 转变。正如通过减少巨噬细胞浸润和 JNK/c-Jun 信号传导所观察到的那样,α-生育酚降低了炎症水平。较低的炎症状态与 CHOP 和 Bax 表达以及纤维化相关的 COL1A1 和 α-SMA 水平的降低同时发生。总之,除了 JNK/CHOP/细胞凋亡信号之外,α-生育酚补充剂还通过降低 JNK/c-Jun/炎症轴来抑制胆固醇诱导的 NASH 发展,这可能有助于抵抗 NAFLD/NASH 转变。正如通过减少巨噬细胞浸润和 JNK/c-Jun 信号传导所观察到的那样,α-生育酚降低了炎症水平。较低的炎症状态与 CHOP 和 Bax 表达以及纤维化相关的 COL1A1 和 α-SMA 水平的降低同时发生。总之,除了 JNK/CHOP/细胞凋亡信号之外,α-生育酚补充剂还通过降低 JNK/c-Jun/炎症轴来抑制胆固醇诱导的 NASH 发展,这可能有助于抵抗 NAFLD/NASH 转变。
更新日期:2021-06-22
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