Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice.
Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice.
复制标题
激活腺苷单磷酸激活的蛋白激酶介导小鼠的成纤维细胞生长因子1免受非酒精性脂肪肝病的保护。
DOI：
10.1002/hep.31568
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Tan Y
中科院分区：
文献类型：
--
作者：
Lin Q;Huang Z;Cai G;Fan X;Yan X;Liu Z;Zhao Z;Li J;Li J;Shi H;Kong M;Zheng MH;Conklin DJ;Epstein PN;Wintergerst KA;Mohammadi M;Cai L;Li X;Li Y;Tan Y
成纤维细胞生长因子1（FGF1）通过不确定的机制显示了2型糖尿病和肥胖小鼠中非酒精脂肪肝疾病（NAFLD）的保护。
FGF1ΔHBS在9个月的DB/DB小鼠中有效，肝脏重量，脂质沉积和炎症下降，肝损伤通过刺激核因子核因子2与2（NRF2）的核易位来减少氧化物。抗氧化剂蛋白表达的升高。 AMP激活的蛋白激酶（AMPK）及其底物的底物研究表明，NAFLD样的氧化损伤和脂质积累可以被FGF1ΔHB逆转。 - 氧化作用，但不改善脂质代谢。废除的FGF1ΔHB在氧化应激和脂质代谢中受益于FGF受体4（FGFR4），这是对这些体外发现的进一步支持。此外，肝脂肪变性。 E淘汰小鼠。
这些发现表明，FGF1ΔHBS有效预防和逆转肝脏脂肪变性和脂肪性肝炎，并通过通过肝细胞FGFR4激活AMPK来起作用。
Fibroblast growth factor 1 (FGF1) demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a non-mitogenic FGF1 variant (FGF1ΔHBS) against NAFLD. FGF1ΔHBS administration was effective in 9-month old db/db mice with NAFLD; liver weight, lipid deposition and inflammation declined and liver injury decreased. FGF1ΔHBS reduced oxidative stress by stimulating nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1ΔHBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of AMP-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1ΔHBS. In palmitate-treated hepatic cells, siRNA knockdown of Nrf2 abolished only FGF1ΔHBS anti-oxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1ΔHBS benefits on both oxidative stress and lipid metabolism that were FGF receptor 4 (FGFR4) dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1ΔHBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1ΔHBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. These findings indicate that FGF1ΔHBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK via hepatocyte FGFR4.
登录
查看更多内容
DOI：
10.1016/j.bbrc.2018.05.121
发表时间：
2018-07-07
影响因子：
3.1
作者：
Li, Xin;Wu, Di;Tian, Ye
通讯作者：
Tian, Ye
影响因子：
6.6
作者：
Mo, Chunfen;Wang, Ling;Xiao, Hengyi
通讯作者：
Xiao, Hengyi
影响因子：
3
作者：
Korc M;Friesel RE
通讯作者：
Friesel RE
影响因子：
7.7
作者：
Huang, Xinqiang;Yang, Chaofeng;McKeehan, Wallace L.
通讯作者：
McKeehan, Wallace L.
DOI：
10.2741/4218
发表时间：
2014-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Shirwany NA;Zou MH
通讯作者：
Zou MH