title: HCV core-induced nonobese hepatic steatosis is associated with hypoadiponectinemia and is ameliorated by adiponectin administration.
abstract: 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.
authors.affiliation: Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linko, Taiwan. mlchang8210@gmail.com
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.forename: Huei-Chung
authors.initials: HC
authors.lastname: Yeh
authors.forename: Yung-Kuan
authors.initials: YK
authors.lastname: Tsou
authors.forename: Chao-Jan
authors.initials: CJ
authors.lastname: Wang
authors.forename: Hsiao-Yang
authors.initials: HY
authors.lastname: Cheng
authors.forename: Chang-Mu
authors.initials: CM
authors.lastname: Sung
authors.forename: Yu-Pin
authors.initials: YP
authors.lastname: Ho
authors.forename: Tsung-Hsing
authors.initials: TH
authors.lastname: Chen
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000008:administration & dosage* / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015536:Down-Regulation; D005234:Fatty Liver / Q000097:blood* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000378:metabolism; D007150:Immunohistochemistry; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D013623:Tail; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D020738:Leptin; D008055:Lipids; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus