title: Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling.
abstract: OBJECTIVE
  It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes.
  
  
  METHODS
  The influence of treatment with HCV core protein (70R or 70Q) on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and triglyceride content was also analyzed. The effects of toll-like receptor (TLR)2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined.
  
  
  RESULTS
  IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%.
  
  
  CONCLUSIONS
  Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Uraki
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan; Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan; Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tameda
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan; Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan; Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan; Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.affiliation: Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D054392:Adipokines; D015850:Interleukin-6; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus