The peroxisome proliferator activated receptor gamma (PPARgamma) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice.
Obese mice that lack leptin receptor (db (-) /db (-)) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db (-) /db (-)), or lean (db ( + ) /db (-)) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.
Holguin
Fernando
F
Emory University and the Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30308, USA. fch5@cdc.gov
Rojas
Mauricio
M
Hart
C Michael
CM
D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D047495:PPAR gamma; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D052242:Adiponectin; D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D020738:Leptin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone