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Editorial
. 2015 Oct;62(4):994-6.
doi: 10.1002/hep.27926. Epub 2015 Jul 23.

Carbohydrate-responsive element-binding protein, Sirtuin 1, and ethanol metabolism: a complicated network in alcohol-induced hepatic steatosis

Suthat Liangpunsakul  1   2
Affiliations
Editorial

Carbohydrate-responsive element-binding protein, Sirtuin 1, and ethanol metabolism: a complicated network in alcohol-induced hepatic steatosis

Suthat Liangpunsakul. Hepatology. 2015 Oct.
No abstract available

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Conflict of interest statement

Conflict of interest: The author did not have anything to disclose regarding the conflict of interest with respect to this manuscript

Figures

Fig 1
Fig 1. Complex mechanisms and the interplay of ChREBP, SIRT1, and ADH in the regulation of alcohol and lipid metabolism in hepatocytes
The regulation of SIRT1 and ChREBP by alcohol depends on the drinking pattern. Chronic alcohol drinking inhibits SIRT1, through miR-217/lipin 1, which leads to an increase in the acetylated form of SREBP-1c and activation of lipogenic genes, , . In contrast to chronic alcohol drinking, which induces ChREBP activity through dephosphorylation, binge drinking induces ChREBP through acetylation. Acetylated-ChREBP (ChREBPAC) binds to the SIRT1 promoter and inhibits its activity. A decrease in SIRT1 activity is proposed to activate ADH activity through increased acetylation. This results in the acceleration of alcohol metabolism, increasing intrahepatic acetaldehyde, and ChREBPAC. ChREBPAC can directly activate lipogenic genes or further inhibit SIRT1, leading to a vicious cycles which eventually aggravate the progression of ALD in binge drinkers. Activating SIRT1 with compound such as resveratrol can de-acetylate ADH and increase the risk of alcohol intoxication through the inhibition of alcohol metabolism, as shown in red. This leads to the therapeutic dilemma of using SIRT1 activators as the therapeutic potential for the treatment of ALD, especially in binge drinkers.
See this image and copyright information in PMC

Comment on

References

    1. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141(5):1572–1585. - PMC - PubMed
    1. You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP) J Biol Chem. 2002;277(32):29342–29347. - PubMed
    1. Yin H, Hu M, Zhang R, Shen Z, Flatow L, You M. MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1. J Biol Chem. 2012;287(13):9817–9826. - PMC - PubMed
    1. Yin H, Hu M, Liang X, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver. Gastroenterology. 2014;146(3):801–811. - PMC - PubMed
    1. Xu X, So JS, Park JG, Lee AH. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Semin Liver Dis. 2013;33(4):301–311. - PMC - PubMed

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