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The Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Ligand Rosiglitazone Modulates Bronchoalveolar Lavage Levels of Leptin, Adiponectin, and Inflammatory Cytokines in Lean and Obese Mice

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Abstract

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 (PPARγ) 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.

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Acknowledgments

The authors acknowledge their grant support from the Veterans Affairs Research Service, the National Institutes of Health, and Takeda Pharmaceuticals. The expert technical assistance of Mr. Dean Kleinhenz, Ms. Jennifer Bland, and Mrs. Heidi Thorson is gratefully acknowledged.

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Authors and Affiliations

  1. Emory University and the Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, 30308, USA

    Fernando Holguin, Mauricio Rojas & C. Michael Hart

  2. Davis Fisher Bldg., Clinical Research Center, 550 Peachtree Street NE, 2nd Floor, Room 2331, Atlanta, GA, 30308, USA

    Fernando Holguin

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Correspondence to Fernando Holguin.

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Holguin, F., Rojas, M. & Hart, C.M. The Peroxisome Proliferator Activated Receptor Gamma (PPARγ) Ligand Rosiglitazone Modulates Bronchoalveolar Lavage Levels of Leptin, Adiponectin, and Inflammatory Cytokines in Lean and Obese Mice. Lung 185, 367–372 (2007). https://doi.org/10.1007/s00408-007-9035-9

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  • DOI: https://doi.org/10.1007/s00408-007-9035-9

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