Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide yet
there are currently no effective pharmacologic treatment options available [
[1]
]. More importantly, liver transplantation remains the only definitive treatment for
end-stage liver failure [
[2]
]. The clinical manifestations of ALD exist as a spectrum of mild to severe disease
ranging from simple steatosis to alcoholic hepatitis and cirrhosis [
[3]
]. The pathophysiology of ALD remains poorly understood, but is believed to be a combination
of various stressors such as oxidative and ER stress, inflammation and a disruption
of the gut-liver barrier [
[4]
,
[5]
]. The difficulty in developing viable treatment options for ALD lies in part in its
pathologic complexity and a lack of an effective mouse model that can recapitulate
the full spectrum of human disease. This is especially true for advanced stages of
ALD where there are currently no reliable mouse models that can consistently reproduce
alcohol-induced liver fibrosis.To read this article in full you will need to make a payment
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References
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- FXR and TGR5 agonists ameliorate liver injury, steatosis, and inflammation after binge or prolonged alcohol feeding in mice.Hepatol Commun. 2018; 2: 1379-1391
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Article info
Publication history
Published online: April 25, 2019
Received:
March 27,
2019
Footnotes
☆Portions of these discussed studies were supported by Baylor Scott & White Institute, the Hickam Endowed Chair, Gastroenterology, Medicine, Indiana University, a VA Research Senior Career Scientist Award.
☆☆The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.
Identification
Copyright
Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
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- The role of sphingosine kinase 2 in alcoholic liver diseaseDigestive and Liver DiseaseVol. 51Issue 8
- PreviewAlcoholic liver disease (ALD) is one of the most common liver diseases worldwide. However, the exact mechanisms underlying ALD remain unclear. Previous studies reported that sphingosine kinase 2 (SphK2) plays an essential role in regulating hepatic lipid metabolism. In the current study, we demonstrate that compared to wild-type (WT) mice, SphK2 deficient (SphK2−/−) mice exhibited a greater degree of liver injury and hepatic lipid accumulation after feeding with an alcohol diet for 60 days. This is accompanied by a down-regulation of steroid 7-alpha-hydroxylase (Cyp7b1) and an up-regulation of pro-inflammatory mediators (Tnfα, F4/80, Il-1β).
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