Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease.
OBJECTIVE
This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD).


METHODS
Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and DL-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.


RESULTS
Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P < 0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P < 0.02) and decreased hepatic steatosis (P < 0.01), hepatic triglyceride levels (P < 0.01), hepatic-conjugated dienes (CD; P < 0.02) and serum ALT levels (P < 0.002) at 12 weeks. Reduced hepatic steatosis (P < 0.005) and CD (P < 0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content.


CONCLUSIONS
Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.
Kirsch
Richard
R
Department of Anatomical Pathology, University of Cape Town, Cape Town, South Africa. rkirsch@mtsinai.on.ca
Sijtsema
Helene P
HP
Tlali
Mpho
M
Marais
Adrian D
AD
Hall
Pauline de la M
Pde L
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D002796:Choline Deficiency / Q000150:complications; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D019190:Iron Overload / Q000150:complications*; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008715:Methionine / Q000172:deficiency; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344
D008715:Methionine; D000410:Alanine Transaminase; D006909:Hydroxyproline