Background
Recent evidence demonstrates that alcohol activates the mechanistic target of rapamycin (mTOR) and impairs hepatic transcription factor EB (TFEB) reducing autophagy and contributing to alcohol-induced liver injury. Trehalose, a disaccharide, activates TFEB and protects against diet-induced nonalcoholic fatty liver disease in mice. The
Conclusions
Trehalose fails to improve the impaired TFEB induced by Gao-binge alcohol and does not protect against alcohol-induced liver injury.
Methods
Male C57BL/6J mice were subjected to chronic-plus-binge (Gao-binge) alcohol feeding with and without trehalose supplementation. Some mice were also administrered Alda-1, an aldehyde dehydrogenase 2 agonist.
Results
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. However, trehalose did not improve the impairment in 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 the infiltration of hepatic neutrophils and inflammatory cytokine gene expression in Gao-binge alcohol-fed mice livers. Conclusions: Trehalose fails to improve the impaired TFEB induced by Gao-binge alcohol and does not protect against alcohol-induced liver injury.