The adiponectin-SIRT1-AMPK pathway in alcoholic fatty liver disease in the rat.
Alcohol Clin Exp Res
; 39(3): 424-33, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25703252
ABSTRACT
BACKGROUND:
Our previous work showed that binge drinking in the rat induced hepatic steatosis which correlated with reduced expression of AMP-activated protein kinase (AMPK). In this study, we used the rat model to investigate the role of adiponectin (Adip), sirtuin 1 (SIRT1), AMPK, and lipin 1 (LIP 1) signaling, a central controlling pathway of lipid metabolism in hepatic steatosis.METHODS:
The serum Adip and tumor necrosis factor-alpha (TNF-α) as well as liver Adip receptors (AdipoR1 and AdipoR2) SIRT1, AMPK, phosphorylated AMPK (p-AMPK), sterol regulatory element-binding proteins (SREBPs), acetyl-CoA carboxylase (ACC), LIP 1, lipocalin-2 (LCN2), and serum amyloid A1 were assessed in the rat model where 16 weeks of gavaged alcohol were administered.RESULTS:
In this model of ethanol (EtOH) administration, hepatic steatosis, necrosis, as well as inflammation were increased over the 16-week period. The level of TNF-α in the serum was increased while the Adip content decreased significantly, and there was an inverse relationship between the content of TNF-α and Adip. The mRNA and protein expression of AdipoR2, SIRT1, and AMPK was suppressed by EtOH in the rats' hepatic tissue. Additionally, EtOH significantly decreased p-AMPK by 90% over the 16-week period. In parallel, there was a 2.53- and 1.82-fold increase of lipogenic genes SREBP1c and ACC, and a 3.22- and 4.12-fold increase of LIP 1 and LIP 1 ß mRNA expression, respectively, in the hepatic tissue of the rats.CONCLUSIONS:
Our present observations demonstrate that the impaired Adip-SIRT1-AMPK signaling pathway contributes, at least in part, to the development of alcoholic fatty liver disease in EtOH binge rats.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Etanol
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Adiponectina
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Proteínas Quinases Ativadas por AMP
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Fígado Gorduroso Alcoólico
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Sirtuína 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article