Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection.
BACKGROUND
Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis.


OBJECTIVE
To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown.


METHODS
We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma 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-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, 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-gamma 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.
de Gottardi
A
A
Services de Gastroentérologie et d'Hépatologie, Hopitaux Universitaires, Geneva, Switzerland. andrea.degottardi@medcli.unige.ch
Pazienza
V
V
Pugnale
P
P
Bruttin
F
F
Rubbia-Brandt
L
L
Juge-Aubry
C E
CE
Meier
C A
CA
Hadengue
A
A
Negro
F
F
D000328:Adult; D005234:Fatty Liver / Q000378:metabolism* / Q000821:virology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger