Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.
PLoS One
; 13(10): e0205747, 2018.
Article
em En
| MEDLINE
| ID: mdl-30379862
Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 µmol/L) and NASH (1.51 ± 0.56 µmol/L) compared to LD (1.21 ± 0.38 µmol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina A
/
Regulação da Expressão Gênica
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Hepatopatia Gordurosa não Alcoólica
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Fígado
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prevalence_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos