title: Blockade of interleukin 6 signalling ameliorates systemic insulin resistance through upregulation of glucose uptake in skeletal muscle and improves hepatic steatosis in high-fat diet fed mice.
abstract: OBJECTIVE
  Mice fed high-fat diet (HFD) demonstrate obesity-related systemic insulin resistance (IR). Aim of this study is to clarify the role of interleukin (IL)-6 in IR in vivo focusing on skeletal muscle, adipose tissue and liver.
  
  
  METHODS
  Plasma markers of IR and hepatic IL-6 signalling were examined in eight-week HFD feeding C57/BL6 mice. Furthermore, IR-related molecules in skeletal muscles, adipose tissues and livers were investigated following a single injection of anti- IL-6 receptor neutralizing antibody (MR16-1) in two-week HFD feeding mice. To investigate the role of IL-6 in hepatic steatosis by prolonged HFD, hepatic triglyceride accumulation was assessed in eight-week HFD feeding mice with continuous MR16-1 treatment.
  
  
  RESULTS
  High-fat diet for both 2 and 8 weeks elevated plasma IL-6, insulin and leptin, which were decreased by MR16-1 treatment. A single injection of MR16-1 ameliorated IR as assessed by glucose and insulin tolerance test, which may be attributable to upregulation of glucose transporter type 4 via phosphorylation of AMP-activated protein kinase as well as upregulation of peroxisome proliferator-activated receptor alpha in livers and, particularly, in skeletal muscles. MR16-1 also decreased mRNA expression of leptin and tumour necrosis factor-alpha and increased that of adiponectin in adipose tissue. High-fat diet for 8 weeks, not 2 weeks, induced hepatic steatosis and increased hepatic triglyceride content, all of which were ameliorated by MR16-1 treatment.
  
  
  CONCLUSIONS
  Blockade of excessive IL-6 stimulus ameliorated HFD-induced IR in a skeletal muscle and modulated the production of adipokines from an early stage of NAFLD, leading to prevention of liver steatosis for a long term.
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Kanji
authors: K
authors: Yamaguchi
authors: Takeshi
authors: T
authors: Nishimura
authors: Hiroshi
authors: H
authors: Ishiba
authors: Yuya
authors: Y
authors: Seko
authors: Akira
authors: A
authors: Okajima
authors: Hideki
authors: H
authors: Fujii
authors: Nozomi
authors: N
authors: Tochiki
authors: Atsushi
authors: A
authors: Umemura
authors: Michihisa
authors: M
authors: Moriguchi
authors: Yoshio
authors: Y
authors: Sumida
authors: Hironori
authors: H
authors: Mitsuyoshi
authors: Kohichiroh
authors: K
authors: Yasui
authors: Masahito
authors: M
authors: Minami
authors: Takeshi
authors: T
authors: Okanoue
authors: Yoshito
authors: Y
authors: Itoh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing; D017931:DNA Primers / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000503:physiopathology / Q000517:prevention & control*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D019947:Receptors, Interleukin-6 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
chemical_list: D057134:Antibodies, Neutralizing; D017931:DNA Primers; D051275:Glucose Transporter Type 4; D015850:Interleukin-6; D047493:PPAR alpha; D019947:Receptors, Interleukin-6; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: HFD; IL-6; NAFLD; STAT3; insulin resistance; leptin