TY - JOUR
T1 - Peroxisome proliferator-activated receptor-α and -γ mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection
AU - De Gottardi, A.
AU - Pazienza, V.
AU - Pugnale, P.
AU - Bruttin, F.
AU - Rubbia-Brandt, L.
AU - Juge-Aubry, C. E.
AU - Meier, C. A.
AU - Hadengue, A.
AU - Negro, F.
PY - 2006/1
Y1 - 2006/1
N2 - Background: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. Aim: To assess the contribution of peroxisome proliferator-activated receptor-α and -γ to the pathogenesis of hepatitis C virus associated steatosis is unknown. Methods: We measured peroxisome proliferator-activated receptor (PPAR)-α and -γ mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. Results: PPAR-α mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-α in genotype 1, but not in genotype 3. PPAR-γ expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-γ, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-γ mRNA compared with hepatitis C virus 1b. Conclusions: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.
AB - Background: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. Aim: To assess the contribution of peroxisome proliferator-activated receptor-α and -γ to the pathogenesis of hepatitis C virus associated steatosis is unknown. Methods: We measured peroxisome proliferator-activated receptor (PPAR)-α and -γ mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. Results: PPAR-α mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-α in genotype 1, but not in genotype 3. PPAR-γ expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-γ, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-γ mRNA compared with hepatitis C virus 1b. Conclusions: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.
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U2 - 10.1111/j.1365-2036.2006.02729.x
DO - 10.1111/j.1365-2036.2006.02729.x
M3 - Article
C2 - 16393287
AN - SCOPUS:33644882808
VL - 23
SP - 107
EP - 114
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
SN - 0269-2813
IS - 1
ER -