Title
PPAR<tex>$\alpha$</tex> gene expression correlates with severity and histological treatment response in patients with Non-alcoholic Steatohepatitis PPAR<tex>$\alpha$</tex> gene expression correlates with severity and histological treatment response in patients with Non-alcoholic Steatohepatitis
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
University Hospital Antwerp
Publication type
article
Publication
Amsterdam ,
Subject
Human medicine
Source (journal)
Journal of hepatology. - Amsterdam
Volume/pages
63(2015) :1 , p. 164-173
ISSN
0168-8278
ISI
000356314400022
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background and aims Peroxisome proliferator-activated receptors (PPARs) have been implicated in NASH pathogenesis, mainly based on animal data. Gene expression data in NASH patients are scarce. We studied liver PPARα, β/δ and γ expression in a large cohort of obese patients assessed for presence of NAFLD at baseline and 1 year follow-up. Methods Patients presenting to the obesity clinic underwent a hepatic work-up. If NAFLD was suspected, liver biopsy was performed. Gene expression was studied by mRNA quantification. Patients were reassessed after 1 year. Results 125 patients were consecutively included with follow-up including liver biopsy in n=85. Liver PPARα expression negatively correlated with presence of NASH (p=0.001) and with severity of steatosis (p=0.003), ballooning (p=0.001), NASH activity score (p=0.008) and fibrosis (p=0.003). PPARα expression was positively correlated to adiponectin (R2=0.345, p=0.010) and inversely correlated to visceral fat (R2=-0.343, p<0.001), HOMA IR (R2=-0.411, p<0.001) and CK18 (R2=-0.233, p=0.012). Liver PPARβ/δ and PPARγ expression did not correlate with any histological feature nor with glucose metabolism or serum lipids. At 1 year, correlation of PPARα expression with liver histology was confirmed. In longitudinal analysis, an increase in expression of PPARα and its target genes was significantly associated with histological improvement (p=0.008). Conclusion Human liver PPARα gene expression negatively correlates with NASH severity, visceral adiposity and insulin resistance and positively with adiponectin. Histological improvement is associated with an increase in expression of PPARα and its target genes. These data might suggest that PPARα is a potential therapeutic target in NASH.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/da346c/9f747d35.pdf
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