title: Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Organ-specific IR in the liver (hepatic glucose production (HGP) × fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-2H2]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively.
  
  
  RESULTS
  HGP × FPI was significantly correlated with Rd (r =  -0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r =  -0.47, P<0.001) as well as with HGP × FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r =  -0.32, P<0.05). IMCL was not associated with Rd (r =  -0.16, P = 0.26). Fat mass and its percentage were associated with HGP × FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r =  -0.59, P<0.001; r =  -0.52, P<0.001, respectively), but not with %FFA (r =  -0.21, P = 0.10; r =  -0.001, P = 0.99, respectively).
  
  
  CONCLUSIONS
  Unexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle.
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Takamura
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Yumie
authors.initials: Y
authors.lastname: Takeshita
authors.affiliation: Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Misu
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Tsuguhito
authors.initials: T
authors.lastname: Ota
authors.affiliation: Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Kumpei
authors.initials: K
authors.lastname: Tokuyama
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Jichi Medical University, Shimono, Tochigi, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Nagasaka
authors.affiliation: Clinical Research Center for Diabetes, Tokushima University, Tokushima, Tokushima, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.affiliation: Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D050154:Adiposity; D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007564:Japan; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000473:pathology*; D009928:Organ Specificity; D012044:Regression Analysis
chemical_list: D007328:Insulin; D005947:Glucose