title: Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db mice.
abstract: OBJECTIVE
  Recently, adipose tissue inflammation induced by macrophage infiltration through MCP-1/C-C chemokine receptor-2 (CCR2) pathway is considered to play a role in the development of visceral obesity and insulin resistance. In the present study, to further examine the role of CCR2 in the development of obesity and type 2 diabetes, we studied the effect of pharmacological inhibition of CCR2 from the early stage of obesity in db/db mice.
  
  
  RESULTS
  Db/+m (lean control) and db/db mice were fed with a standard diet with or without 0.005% propagermanium, as a CCR2 inhibitor for 12 weeks from 6 weeks of age. Propagermanium treatment decreased body weight gain, visceral fat accumulation, and the size of adipocytes only in db/db mice. Further, propagermanium suppressed macrophage accumulation and inflammation in adipose tissue. Propagermanium treatment also ameliorated glucose tolerance and insulin sensitivity, and decreased hepatic triglyceride contents in db/db mice.
  
  
  CONCLUSIONS
  Propagermanium improved obesity and related metabolic disorders, such as insulin resistance and hepatic steatosis by suppressing inflammation in adipose tissue. Our data indicate that inhibition of CCR2 could improve obesity and type 2 diabetes by interfering adipose tissue inflammation, and that propagermanium may be a beneficial drug for the treatment of the metabolic syndrome.
authors.affiliation: Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murayama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Ueda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanamori
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariyasu
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D005857:Germanium; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D009942:Organometallic Compounds / Q000494:pharmacology*; D011422:Propionates; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: C515335:Ccr2 protein, mouse; D009942:Organometallic Compounds; D011422:Propionates; D054390:Receptors, CCR2; D014280:Triglycerides; D005857:Germanium; C066750:propagermanium