Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice

Xiaojuan Chao; Shaogui Wang; Ling Yang; Hong-Min Ni; Wen-Xing Ding

doi:10.1111/acer.14695

Back

Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice

Journal article

Open access

Peer reviewed

Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice

Xiaojuan Chao, Shaogui Wang, Ling Yang, Hong-Min Ni and Wen-Xing Ding

Alcoholism, clinical and experimental research, Vol.45(10), pp.1950-1964

10/2021

DOI: 10.1111/acer.14695

PMCID: PMC8602756

PMID: 34486131

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/8602756View

Open Access

Abstract

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 aim of the present study was to investigate whether trehalose would reverse the impairment of 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 administrered 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. 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. Trehalose fails to improve the impaired TFEB induced by Gao-binge alcohol and does not protect against alcohol-induced liver injury.

Aldehyde Dehydrogenase, Mitochondrial - metabolism

Animals

Autophagy - drug effects

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - agonists

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism

Drug Evaluation, Preclinical

Ethanol - adverse effects

Ethanol - metabolism

Liver - drug effects

Liver - metabolism

Liver Diseases, Alcoholic - prevention & control

Male

Mice

Mice, Inbred C57BL

RAW 264.7 Cells

TOR Serine-Threonine Kinases - metabolism

Trehalose - metabolism

Trehalose - pharmacology

Trehalose - therapeutic use

Details

Title: Subtitle: Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice
Creators: Xiaojuan Chao - University of Kansas Medical Center
Shaogui Wang - University of Kansas Medical Center
Ling Yang - University of Iowa
Hong-Min Ni - University of Kansas Medical Center
Wen-Xing Ding - University of Kansas Medical Center
Resource Type: Journal article
Publication Details: Alcoholism, clinical and experimental research, Vol.45(10), pp.1950-1964
DOI: 10.1111/acer.14695
PMID: 34486131
PMCID: PMC8602756
NLM abbreviation: Alcohol Clin Exp Res
ISSN: 0145-6008
eISSN: 1530-0277
Publisher: Wiley
Grant note: R37 AA020518 / NIAAA NIH HHS R01 DK102142 / NIDDK NIH HHS U01 AA024733 / NIAAA NIH HHS R21 AA027050 / NIAAA NIH HHS P30 DK054759 / NIDDK NIH HHS R01 AG072895 / NIA NIH HHS
Language: English
Date published: 10/2021
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984284349402771

Metrics

12 Record Views

11 Times Cited - Web of Science