title: Exacerbation of insulin resistance and hepatic steatosis deriving from zinc deficiency in patients with HCV-related chronic liver disease.
abstract: The role of zinc (Zn) in hepatic steatosis of patients with HCV-related chronic liver disease (CLD-C) remains uncertain, although persistent HCV infection often evokes hepatic steatosis. The primary purpose of this study was to elucidate the contribution of Zn deficiency to hepatic steatosis in patients with CLD-C. Fifty nondiabetic patients with CLD-C were enrolled. Hepatic 4-hydroxy-2-nonenal (4-HNE) expression was examined using an immunohistochemical procedure as a marker for lipid peroxidation. Serum ferritin levels were assessed for iron overload. Insulin resistance was evaluated using the values of the homeostasis model for assessment of insulin resistance (HOMA-IR). The severity of hepatic steatosis was graded on the classification system proposed by Brunt and colleagues. Serum Zn levels were inversely correlated with serum ferritin levels in the patients with CLD-C (r = -0.382, p = 0.0062). Serum ferritin levels were strongly associated with the HOMA-IR values (r = 0.476, p = 0.0005). Therefore, Zn deficiency resulted in insulin resistance through iron overload. Moreover, serum Zn levels were significantly decreased in proportion to the level of hepatic 4-HNE expression, which was enhanced as hepatic steatosis developed. Then, Zn deficiency eventually seemed to exacerbate hepatic steatosis by way of an increase in lipid peroxidation. However, the serum Zn levels were not associated with either loads of HCV-RNA or HCV genotypes. These data suggest that, in patients with CLD-C, Zn deficiency promotes insulin resistance by exacerbating iron overload in the liver and induces hepatic steatosis by facilitating lipid peroxidation.
authors.affiliation: Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1, Hara, Mure-cho, Takamatsu, Kagawa, 761-0123, Japan, himoto@chs.pref.kagawa.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Himoto
authors.forename: Takako
authors.initials: T
authors.lastname: Nomura
authors.forename: Joji
authors.initials: J
authors.lastname: Tani
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Asahiro
authors.initials: A
authors.lastname: Morishita
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Reiji
authors.initials: R
authors.lastname: Haba
authors.forename: Hisashi
authors.initials: H
authors.lastname: Masugata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015032:Zinc / Q000097:blood* / Q000172:deficiency*
chemical_list: D000447:Aldehydes; D005293:Ferritins; D015032:Zinc; C027576:4-hydroxy-2-nonenal