Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice.
Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice.
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DOI：
10.1111/acer.14695
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Ding WX
中科院分区：
文献类型：
--
作者：
Chao X;Wang S;Yang L;Ni HM;Ding WX
最近的证据表明，酒精激活了雷帕霉素的机械靶点（mTOR），损害了肝转录因子EB（TFEB），导致自噬不足，这有助于酒精诱导的肝损伤。海藻糖是一种二糖，已被证明可以激活TFEB并保护小鼠免受饮食诱导的非酒精性脂肪肝疾病。本研究的目的是研究海藻糖是否可以逆转酒精诱导的TFEB受损，并保护酒精诱导的肝损伤。对雄性C57 BL/6 J小鼠进行慢性加狂欢（Gao-binge）酒精喂养，同时补充和不补充海藻糖。一些小鼠还被给予醛脱氢酶2激动剂Alda-1。我们发现Alda-1不影响高酒精诱导的小鼠肝脏mTOR激活和TFEB受损。海藻糖增加TFEB核转位，小鼠肝脏和培养的AML 12细胞中LC 3-II和溶酶体蛋白水平升高，证实海藻糖激活TFEB。令人惊讶的是，海藻糖没有改善由高酒精诱导的TFEB受损。根据血清丙氨酸氨基转移酶（ALT）水平、组织学分析和肝脏甘油三酯水平，Alda-1和海藻糖均未能保护高酒精诱导的脂肪变性和肝损伤。有趣的是，海藻糖增加了小鼠巨噬细胞RAW264.7细胞中促炎基因的表达，并轻微增加了高酒精小鼠肝脏中肝脏中性粒细胞的浸润和炎症细胞因子基因的表达。海藻糖不能改善高酒精诱导的TFEB受损，也不能保护酒精诱导的肝损伤。
Recent evidence demonstrated that alcohol activates mechanistic target of rapamycin (mTOR) and impairs hepatic transcription factor EB (TFEB) resulting in insufficient autophagy, which contributes to alcohol-induced liver injury. Trehalose, a disaccharide, has been shown to activate TFEB and protects against diet-induced non-alcoholic fatty liver disease in mice. The aim of the present study was to investigate whether trehalose would reverse impaired TFEB induced by alcohol and protect against alcohol-induced liver injury. Male C57BL/6J mice were subjected to chronic-plus-binge (Gao-binge) alcohol feeding with and without trehalose supplementation. Some mice were also administrated with Alda-1, an aldehyde dehydrogenase 2 agonist. We found that Alda-1 did not affect Gao-binge alcohol-induced mTOR activation and impaired TFEB in mouse livers. Trehalose increased TFEB nuclear translocation, elevated levels of LC3-II and lysosomal proteins in mouse livers and cultured AML12 cells, confirming the activation of TFEB by trehalose. Surprisingly, trehalose did not improve impaired TFEB induced by Gao-binge alcohol. Both Alda-1 and trehalose failed to protect against Gao-binge alcohol-induced steatosis and liver injury, based on the serum levels of alanine aminotransferase (ALT), histological analysis and levels of hepatic triglyceride. Interestingly, trehalose increased expression of pro-inflammatory genes in mouse macrophage RAW264.7 cells, and slightly increased infiltration of hepatic neutrophils and inflammatory cytokine gene expression in Gao-binge alcohol fed moues livers. Trehalose fails to improve the impaired TFEB induced by Gao-binge alcohol and does not protect against alcohol-induced liver injury.
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影响因子：
--
作者：
Li Y;Wang S;Ni HM;Huang H;Ding WX
通讯作者：
Ding WX
影响因子：
29.4
作者：
Massey V;Parrish A;Argemi J;Moreno M;Mello A;García-Rocha M;Altamirano J;Odena G;Dubuquoy L;Louvet A;Martinez C;Adrover A;Affò S;Morales-Ibanez O;Sancho-Bru P;Millán C;Alvarado-Tapias E;Morales-Arraez D;Caballería J;Mann J;Cao S;Sun Z;Shah V;Cameron A;Mathurin P;Snider N;Villanueva C;Morgan TR;Guinovart J;Vadigepalli R;Bataller R
通讯作者：
Bataller R
DOI：
10.1111/j.1530-0277.2012.01742.x
发表时间：
2012-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Dolganiuc A;Thomes PG;Ding WX;Lemasters JJ;Donohue TM Jr
通讯作者：
Donohue TM Jr
影响因子：
2.3
作者：
Lu, SC;Mato, JM
通讯作者：
Mato, JM
影响因子：
3.7
作者：
Wu H;Chang Q
通讯作者：
Chang Q