Endogenously increased n-3 PUFA levels in fat-1 transgenic mice do not protect from non-alcoholic steatohepatitis.
Non-alcoholic fatty liver disease (NAFLD)
fat-1
n-6/n-3
non-alcoholic steatohepatitis (NASH)
steatosis
Journal
Hepatobiliary surgery and nutrition
ISSN: 2304-3881
Titre abrégé: Hepatobiliary Surg Nutr
Pays: China (Republic : 1949- )
ID NLM: 101600750
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
entrez:
2
11
2019
pubmed:
2
11
2019
medline:
2
11
2019
Statut:
ppublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis. Possible reasons for the NAFLD epidemic in industrialized countries are the high intake of pro-inflammatory n-6 polyunsaturated fatty acids (n-6 PUFAs) and low consumption of healthy n-3 PUFAs. Due to their anti-inflammatory properties, n-3 PUFAs may have the potential to alleviate chronic liver disease. Herein, we examined the therapeutic effect of increased n-3 PUFA tissue levels in fat-1 transgenic mice on progressive NASH. Disease was induced in mice by streptozotocin and high fat diet (STZ/HFD) resulting in NASH. NAFLD in 6 and 8 weeks old wild type and fat-1 transgenic STZ/HFD treated mice was analyzed. Unlike all other mammals, fat-1 transgenic mice ubiquitously express an n-3 fatty acid desaturase, which converts n-6 to n-3 PUFAs, leading to increased n-3 and decreased n-6 PUFA tissue contents. Liver damage, NAFLD activity score (NAS), hepatic lipid accumulation and inflammation were significantly reduced in fat-1 transgenic STZ/HFD treated mice in the early (6 weeks) but not late (8 weeks) phase of NASH. Simultaneously, mRNA expression of genes involved in fatty acid uptake and storage ( Endogenously elevated n-3 PUFA levels in fat-1 transgenic mice transiently delay the onset of STZ/HFD induced NASH but failed to efficiently protect from NASH development.
Sections du résumé
BACKGROUND
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis. Possible reasons for the NAFLD epidemic in industrialized countries are the high intake of pro-inflammatory n-6 polyunsaturated fatty acids (n-6 PUFAs) and low consumption of healthy n-3 PUFAs. Due to their anti-inflammatory properties, n-3 PUFAs may have the potential to alleviate chronic liver disease. Herein, we examined the therapeutic effect of increased n-3 PUFA tissue levels in fat-1 transgenic mice on progressive NASH.
METHODS
METHODS
Disease was induced in mice by streptozotocin and high fat diet (STZ/HFD) resulting in NASH. NAFLD in 6 and 8 weeks old wild type and fat-1 transgenic STZ/HFD treated mice was analyzed. Unlike all other mammals, fat-1 transgenic mice ubiquitously express an n-3 fatty acid desaturase, which converts n-6 to n-3 PUFAs, leading to increased n-3 and decreased n-6 PUFA tissue contents.
RESULTS
RESULTS
Liver damage, NAFLD activity score (NAS), hepatic lipid accumulation and inflammation were significantly reduced in fat-1 transgenic STZ/HFD treated mice in the early (6 weeks) but not late (8 weeks) phase of NASH. Simultaneously, mRNA expression of genes involved in fatty acid uptake and storage (
CONCLUSIONS
CONCLUSIONS
Endogenously elevated n-3 PUFA levels in fat-1 transgenic mice transiently delay the onset of STZ/HFD induced NASH but failed to efficiently protect from NASH development.
Identifiants
pubmed: 31673534
doi: 10.21037/hbsn.2019.04.03
pii: hbsn-08-05-447
pmc: PMC6791993
doi:
Types de publication
Journal Article
Langues
eng
Pagination
447-458Informations de copyright
2019 Hepatobiliary Surgery and Nutrition. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors have no conflicts of interest to declare.
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