Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients.
Acetyl-CoA Carboxylase
/ genetics
Adipose Tissue
/ pathology
Adult
Aged
Biopsy
CD36 Antigens
/ genetics
Carnitine O-Palmitoyltransferase
/ genetics
Coenzyme A Ligases
/ genetics
Disease Progression
Fatty Acid Synthase, Type I
/ genetics
Fatty Acid Transport Proteins
/ genetics
Fatty Acid-Binding Proteins
/ genetics
Fatty Acids, Nonesterified
/ blood
Female
Gene Expression
Humans
Liver Cirrhosis
/ etiology
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
/ complications
PPAR alpha
/ genetics
Prospective Studies
RNA, Messenger
/ metabolism
Time Factors
Burnout nonalcoholic steatohepatitis
Carnitine palmitoyltransferase 1A
Cirrhosis
Fatty acid transport protein 5
Nonalcoholic fatty liver disease
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
21
05
2019
accepted:
19
09
2019
pubmed:
12
10
2019
medline:
1
6
2021
entrez:
12
10
2019
Statut:
ppublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression. Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018. The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss. Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.
Sections du résumé
BACKGROUND
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression.
METHODS
METHODS
Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018.
RESULTS
RESULTS
The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss.
CONCLUSIONS
CONCLUSIONS
Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.
Identifiants
pubmed: 31602526
doi: 10.1007/s00535-019-01633-2
pii: 10.1007/s00535-019-01633-2
doi:
Substances chimiques
CD36 Antigens
0
FABP1 protein, human
0
Fatty Acid Transport Proteins
0
Fatty Acid-Binding Proteins
0
Fatty Acids, Nonesterified
0
PPAR alpha
0
RNA, Messenger
0
SLC27A5 protein, human
0
CPT1A protein, human
EC 2.3.1.21
Carnitine O-Palmitoyltransferase
EC 2.3.1.21
FASN protein, human
EC 2.3.1.85
Fatty Acid Synthase, Type I
EC 2.3.1.85
Coenzyme A Ligases
EC 6.2.1.-
long-chain-fatty-acid-CoA ligase
EC 6.2.1.3
ACACA protein, human
EC 6.4.1.2
Acetyl-CoA Carboxylase
EC 6.4.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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