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Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease

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 t...

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Autores principales: Pettinelli, Paulina, Arendt, Bianca M., Teterina, Anastasia, McGilvray, Ian, Comelli, Elena M., Fung, Scott K., Fischer, Sandra E., Allard, Johane P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209208/
https://www.ncbi.nlm.nih.gov/pubmed/30379862
http://dx.doi.org/10.1371/journal.pone.0205747
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author Pettinelli, Paulina
Arendt, Bianca M.
Teterina, Anastasia
McGilvray, Ian
Comelli, Elena M.
Fung, Scott K.
Fischer, Sandra E.
Allard, Johane P.
author_facet Pettinelli, Paulina
Arendt, Bianca M.
Teterina, Anastasia
McGilvray, Ian
Comelli, Elena M.
Fung, Scott K.
Fischer, Sandra E.
Allard, Johane P.
author_sort Pettinelli, Paulina
collection PubMed
description 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.
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spelling pubmed-62092082018-11-19 Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease Pettinelli, Paulina Arendt, Bianca M. Teterina, Anastasia McGilvray, Ian Comelli, Elena M. Fung, Scott K. Fischer, Sandra E. Allard, Johane P. PLoS One Research Article 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. Public Library of Science 2018-10-31 /pmc/articles/PMC6209208/ /pubmed/30379862 http://dx.doi.org/10.1371/journal.pone.0205747 Text en © 2018 Pettinelli et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pettinelli, Paulina
Arendt, Bianca M.
Teterina, Anastasia
McGilvray, Ian
Comelli, Elena M.
Fung, Scott K.
Fischer, Sandra E.
Allard, Johane P.
Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title_full Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title_fullStr Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title_full_unstemmed Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title_short Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
title_sort altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209208/
https://www.ncbi.nlm.nih.gov/pubmed/30379862
http://dx.doi.org/10.1371/journal.pone.0205747
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