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Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2021 Mar; Vol. 64 (3), pp. 357-367. - Publication Year :
- 2021
-
Abstract
- 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-β1 (transforming growth factor-β1) 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-β1, IL-1β, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-β1-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-β1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro -stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-β1 expression, supporting the suppressive effect of VitD for TGF-β1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-β1, 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.
- Subjects :
- Animals
Biomarkers metabolism
Body Weight drug effects
Cells, Cultured
Cytokines metabolism
Diet, High-Fat
Dietary Supplements
Epithelial-Mesenchymal Transition drug effects
Glucose Tolerance Test
Inflammation pathology
Insulin metabolism
Leptin blood
Lung metabolism
Lung pathology
Male
Methacholine Chloride
Mice, Inbred C57BL
Mice, Transgenic
Obesity blood
Pulmonary Fibrosis blood
Receptors, Calcitriol metabolism
Renin blood
Renin-Angiotensin System drug effects
Respiratory Hypersensitivity blood
Transforming Growth Factor beta1 metabolism
Vitamin D analogs & derivatives
Vitamin D blood
Vitamin D pharmacology
Vitamin D Deficiency blood
Mice
Obesity complications
Pulmonary Fibrosis etiology
Respiratory Hypersensitivity etiology
Vitamin D Deficiency etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 64
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 33296297
- Full Text :
- https://doi.org/10.1165/rcmb.2020-0086OC