Premium
HCV Core‐Induced Nonobese Hepatic Steatosis Is Associated With Hypoadiponectinemia and Is Ameliorated by Adiponectin Administration
Author(s) -
Chang MingLing,
Yeh HueiChung,
Tsou YungKuan,
Wang ChaoJan,
Cheng Hsiaoyang,
Sung ChangMu,
Ho YuPin,
Chen TsungHsing,
Yeh ChauTing
Publication year - 2012
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2012.45
Subject(s) - steatosis , adiponectin , medicine , leptin , endocrinology , adipokine , fatty liver , obesity , insulin resistance , disease
Obesity‐related hepatic steatosis is commonly associated with central fat accumulation and alterations in adipocytokine secretion; however, the connection between nonobese hepatic steatosis and adipocytokines remains unclear. We aim to investigate this connection using an animal model of conditional hepatitis C virus (HCV) core‐transgenic mice. Double transgenic mice (DTM) with doxycycline (dox)‐regulated hepatic overexpression of the HCV core protein were fed standard rodent chow ad libitum following 1 month of a dox‐rich diet. The mice exhibited nonobese hepatic steatosis at 2 months of age. The levels of leptin and adiponectin were assessed in 2‐month‐old DTM (i.e., HCV core‐tetracycline transactivator (tTA)) and single transgenic mice (STM; i.e., tTA). The total fat mass and the body fat distribution of the mice were evaluated using dual‐energy X‐ray absorptiometry (DEXA) and magnetic resonance imaging (MRI). Microarray analyses and quantitative real‐time PCR were conducted using RNA obtained from the visceral fat of paired DTM and STM. Adiponectin was administered intraperitoneally to the 2‐month‐old DTM. No significant differences of the various fat components were noted between the DTM and STM. Leptin mRNA was downregulated in the visceral fat of DTM ( P = 0.011), and serum adiponectin protein levels were reduced in the DTM compared with those in the STM ( P = 0.035). Adiponectin treatment also significantly ameliorated hepatic steatosis in the DTM compared to the controls ( P = 0.024). In conclusion, HCV core‐induced nonobese hepatic steatosis is associated with downregulation of the leptin gene in visceral fat and concurrent hypoadiponectinemia; however, these effects may be ameliorated by adiponectin treatment.