Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human

Holly Vanni, Angeliki Kazeros, Rui Wang, Ben Gary Harvey, Barbara Ferris, Bishnu P. De, Brendan J. Carolan, Ralf Harto Hübner, Timothy P. O'Connor, Ronald Crystal

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1197-1208
Number of pages12
JournalChest
Volume135
Issue number5
DOIs
Publication statusPublished - 1 May 2009
Externally publishedYes

Fingerprint

Epithelium
Smoking
Fats
Genes
Adipose Tissue
Up-Regulation
Lipolysis
Microarray Analysis
Body Weight
Neuroendocrine Cells
Cachexia
Proteins
Bronchoscopy
Smoking Cessation
Smoke
Tobacco Products
Weight Gain
Zinc
Weight Loss
Glycoproteins

Keywords

  • Airway epithelium
  • AZGP1
  • Gene expression
  • Smoking
  • Weight loss

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Vanni, H., Kazeros, A., Wang, R., Harvey, B. G., Ferris, B., De, B. P., ... Crystal, R. (2009). Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human. Chest, 135(5), 1197-1208. https://doi.org/10.1378/chest.08-1024

Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human. / Vanni, Holly; Kazeros, Angeliki; Wang, Rui; Harvey, Ben Gary; Ferris, Barbara; De, Bishnu P.; Carolan, Brendan J.; Hübner, Ralf Harto; O'Connor, Timothy P.; Crystal, Ronald.

In: Chest, Vol. 135, No. 5, 01.05.2009, p. 1197-1208.

Research output: Contribution to journalArticle

Vanni, H, Kazeros, A, Wang, R, Harvey, BG, Ferris, B, De, BP, Carolan, BJ, Hübner, RH, O'Connor, TP & Crystal, R 2009, 'Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human', Chest, vol. 135, no. 5, pp. 1197-1208. https://doi.org/10.1378/chest.08-1024
Vanni H, Kazeros A, Wang R, Harvey BG, Ferris B, De BP et al. Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human. Chest. 2009 May 1;135(5):1197-1208. https://doi.org/10.1378/chest.08-1024
Vanni, Holly ; Kazeros, Angeliki ; Wang, Rui ; Harvey, Ben Gary ; Ferris, Barbara ; De, Bishnu P. ; Carolan, Brendan J. ; Hübner, Ralf Harto ; O'Connor, Timothy P. ; Crystal, Ronald. / Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human. In: Chest. 2009 ; Vol. 135, No. 5. pp. 1197-1208.
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AU - De, Bishnu P.

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