Ethanol-induced hepatic steatosis is modulated by glycogen level in the liver

Gu, Jin; Zhang, Yongxian; Xu, Daqian; Zhao, Zilong; Zhang, Yuxue; Pan, Yi; Cao, Peijuan; Wang, Zhenzhen; Chen, Yan

doi:10.1194/jlr.m056978

Cited by 31 publications

(16 citation statements)

References 28 publications

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“…The data from these studies suggest that SHP plays a complex role in the pathogenesis of ALD via the regulation of ER stress, homocysteine metabolism, hepatic circadian clock, and ethanol catabolism 82–85 . In addition to lipids, glycogen, which is another form of energy storage in the liver, also has an important role in the control of chronic-plus-binge ethanol-induced liver injury via the regulation of lipid metabolism 86 .…”

Section: New Insights Into the Underlying Mechanisms Of Chronic-plus-mentioning

confidence: 99%

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

et al. 2017

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Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and test therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.

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Section: New Insights Into the Underlying Mechanisms Of Chronic-plus-mentioning

confidence: 99%

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

et al. 2017

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“…ALD is manifested as a broad spectrum of disorders, ranging from simple fatty liver to more severe forms of liver injury, including alcoholic hepatitis, cirrhosis, and superimposed hepatocellular carcinoma . Hepatic steatosis is an early response to alcohol consumption and it happens in more than 90% of heavy drinkers, with about 30% of heavy drinkers developing more severe forms of ALD, such as fibrosis and cirrhosis …”

Section: Introductionmentioning

confidence: 99%

Vitamin D Protects Against Alcohol‐Induced Liver Cell Injury Within an NRF2–ALDH2 Feedback Loop

Zhang

Xue

et al. 2019

Molecular Nutrition Food Res

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Scope Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Oxidative stress induced during the alcohol metabolism plays a crucial role in ALD, and clinical evidence demonstrates the prevalence and risks of vitamin D (VD) deficiency in ALD. This study aims to explore the mechanism of VD administration to ameliorate alcohol‐induced cell injury. Methods and results VD activates NRF2 (nuclear factor erythroid 2 (NF‐E2)‐related factor 2) signals along with upregulation of ALDH2 expression. Knockdown of NRF2 eliminates the protective effects of VD treatment. ALDH2 knockdown not only partially affects this protection, but also mildly reduces NRF2 expression. ALDH2 overexpression enhances ERK phosphorylation and upregulated NRF2 transcription via a newly identified TRE in the exon 1 of NRF2. Conclusion This study provides evidence that VD protects against alcohol‐induced cell injury within an NRF2‐ALDH2 feedback loop. NRF2 induced by VD could transcriptionally upregulate ALDH2 expression to help metabolize alcohol. TRE‐driven transcriptional upregulation of NRF2 through ALDH2‐ERK/MEK signals would further exert the anti‐oxidant effects. The study explores a novel potential protection of VD in alcohol‐induced liver cell injury, and contributes to alcohol‐related liver disease nutritional therapies.

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“…A gene involved in glycogen metabolism that was also found in a previous study was significantly different at 30 min (Glycogen binding subunit 70E) (Kong et al 2010). Glycogen metabolism is an important mediator of the effects of longterm alcohol exposure, such as the development of fatty liver disease in humans (Gu et al 2015). The fact that in the main dataset the vast majority of differences in representation were higher in the presence of ethanol suggests that we are not detecting preferential degradation of transcripts in the presence of ethanol.…”

Section: Differences Between Time Pointsmentioning

confidence: 78%

Dynamic changes in gene expression and alternative splicing mediate the response to acute alcohol exposure in Drosophila melanogaster

Signor

Nuzhdin

2018

Heredity

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Environmental changes typically cause rapid gene expression responses in the exposed organisms, including changes in the representation of gene isoforms with different functions or properties. Identifying the genes that respond to environmental change, including in genotype-specific ways, is an important step in treating the undesirable physiological effects of stress, such as exposure to toxins or ethanol. Ethanol is a unique environmental stress in that chronic exposure results in permanent physiological changes and the development of alcohol use disorders. Drosophila is a classic model for deciphering the mechanisms of the response to alcohol exposure, as it meets the criteria for the development of alcohol use disorders, and has similar physiological underpinnings with vertebrates. Because many studies on the response to ethanol have relied on a priori candidate genes, broad surveys of gene expression and splicing are required and have been investigated here. Further, we expose Drosophila to ethanol in an environment that is genetically, socially, and ecologically relevant. Both expression and splicing differences, inasmuch as they can be decomposed, contribute to the response to ethanol in Drosophila melanogaster. However, we find that while D. melanogaster responds to ethanol, there is very little genetic variation in how it responds to ethanol. In addition, the response to alcohol over time is dynamic, suggesting that incorporating time into studies on the response to the environment is important.

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Ethanol-induced hepatic steatosis is modulated by glycogen level in the liver

Cited by 31 publications

References 28 publications

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

Vitamin D Protects Against Alcohol‐Induced Liver Cell Injury Within an NRF2–ALDH2 Feedback Loop

Dynamic changes in gene expression and alternative splicing mediate the response to acute alcohol exposure in Drosophila melanogaster

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