Obesity-induced vitamin D deficiency contributes to lung fibrosis and airway hyperresponsiveness

Heejae Han, Sook In Chung, Hye Jung Park, Eun Yi Oh, Sung Ryeol Kim, Kyung Hee Park, Jae Hyun Lee, Jung Won Park

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18 Citations (Scopus)


Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effects of VitD supplementation were analyzed using high-fat diet (HFD)-induced obese mice and TGF-b1 (transforming growth factor-b1) triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mice had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-b1, IL-1b, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-b1–overexpressing transgenic mice enhanced macrophages in BAL fluid, lung expression of RAS, epithelial–mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-b1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro–stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-b1 expression, supporting the suppressive effect of VitD for TGF-b1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-b1, and proinflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity.

Original languageEnglish
Pages (from-to)357-367
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number3
Publication statusPublished - 2021 Mar

Bibliographical note

Publisher Copyright:
Copyright © 2021 by the American Thoracic Society.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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