title: Dynamic changes of adiponectin and S100A8 levels by the selective peroxisome proliferator-activated receptor-gamma agonist rivoglitazone.
abstract: OBJECTIVE
  Accumulating evidence indicates that the regimen to increase adiponectin will provide a novel therapeutic strategy for metabolic syndrome. Here, we tested the effect of a potent and selective peroxisome proliferator-activated receptor-γ agonist, rivoglitazone (Rivo), a newly synthesized thiazolidinedione derivative, on adiponectin, insulin resistance, and atherosclerosis.
  
  
  RESULTS
  ob/ob mice, apolipoprotein E knockout (apoE KO) mice, and apoE and adiponectin double knockout mice were administered pioglitazone, Rivo, or no compound. Remarkable elevation of plasma adiponectin was observed, especially in Rivo-treated ob/ob mice. Rivo ameliorated insulin resistance in ob/ob mice and reduced atherosclerotic areas in apoE KO mice compared with the pioglitazone group but failed to decrease atherosclerotic areas in double knockout mice. Among adipose mRNAs, adipose S100A8, which activates Toll-like receptor 4-dependent signal transduction cascades and locates upstream of inflammation, was markedly increased in ob/ob mice, and its increase was completely reversed by Rivo treatment. In RAW264.7 macrophage cells and 3T3-L1 adipocytes, Rivo significantly reduced S100A8 mRNA levels.
  
  
  CONCLUSIONS
  The peroxisome proliferator-activated receptor-γ agonist Rivo remarkably enhanced adiponectin in plasma and decreased adipose S100A8 mRNA levels in obese mice. Rivo treatment apparently ameliorated insulin resistance in ob/ob mice and reduced atherosclerosis in apoE KO mice, partly through adiponectin.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Hiuge-Shimizu
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Ayumu
authors.initials: A
authors.lastname: Hirata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.forename: Kouichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Okuno
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001786:Blood Glucose / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D017382:Reactive Oxygen Species / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001057:Apolipoproteins E; D001786:Blood Glucose; D040501:Calgranulin A; D016207:Cytokines; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D047495:PPAR gamma; D017382:Reactive Oxygen Species; C086145:S100a8 protein, mouse; D045162:Thiazolidinediones; C521549:rivoglitazone; D000077205:Pioglitazone