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Original Research: CIGARETTE SMOKING |

Cigarette Smoking Induces Overexpression of a Fat-Depleting Gene AZGP1 in the Human

Holly Vanni, MD; Angeliki Kazeros, MD; Rui Wang, MD; Ben-Gary Harvey, MD; Barbara Ferris, BS; Bishnu P. De, PhD; Brendan J. Carolan, MD; Ralf-Harto Hübner, MD; Timothy P. O'Connor, PhD; Ronald G. Crystal, MD
Author and Funding Information

*From the Department of Medicine (Drs. Vanni, Kazeros, and Harvey), Division of Pulmonary and Critical Care Medicine, and Genetic Medicine (Drs. Wang, De, Carolan, Hübner, O'Connor, and Crystal, and Ms. Ferris), Weill Medical College of Cornell University, New York, NY.

Correspondence to: Ronald G. Crystal, MD, Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Ave, Box 96, New York, NY 10065; e-mail: geneticmedicine@med.cornell.edu


These studies were supported, in part, by National Institutes of Health grants R01 HL074326, P50 HL084936, and UL1-RR024996; and by the Will Rogers Memorial Fund (Los Angeles, CA).

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(5):1197-1208. doi:10.1378/chest.08-1024
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Background:  Smokers weigh less and have less body fat than nonsmokers. Increased body fat and weight gain are observed following smoking cessation. To assess a possible molecular mechanism underlying the inverse association between smoking and body weight, we hypothesized that smoking may induce the expression of a fat-depleting gene in the airway epithelium, the cell population that takes the brunt of the stress of cigarette smoke.

Methods:  To assess whether smoking up-regulates expression in the airway epithelium of genes associated with weight loss, microarray analysis was used to evaluate genes associated with fat depletion in large airway epithelial samples obtained by fiberoptic bronchoscopy from healthy smokers and healthy nonsmokers. As a candidate gene we further evaluated the expression of α2-zinc-glycoprotein 1 (AZGP1), a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice, is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. AZGP1 protein expression was assessed by Western analysis and localization in the large airway epithelium by immunohistochemistry.

Results:  Both microarray and TaqMan analysis demonstrated that AZGP1 messenger RNA levels were higher in the large airway epithelium of healthy smokers compared to healthy nonsmokers (p < 0.05, all comparisons). Western analysis of airway biopsy specimens from smokers compared with those from nonsmokers demonstrated up-regulation of AZGP1 at the protein level, and immunohistochemical analysis demonstrated up-regulation of AZGP1 in secretory as well as neuroendocrine cells of smokers.

Conclusions:  In the context that AZGP1 is involved in lipolysis and fat loss, its overexpression in the airway epithelium of chronic smokers may represent one mechanism for the weight difference in smokers vs nonsmokers.

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