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Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness

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Title: Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness
Authors: Heejae Han, Sook In Chung, Hye Jung Park, Eun Yi Oh, Sung-Ryeol Kim, Kyung Hee Park, Jae-Hyun Lee, Jung-Won Park
Contributors: Heejae Han, Sook In Chung, Hye Jung Park, Eun Yi Oh, Sung-Ryeol Kim, Kyung Hee Park, Jae-Hyun Lee, Jung-Won Park, Kim, Sung Ryeol
Source: American Journal of Respiratory Cell and Molecular Biology. 64:357-367
Publisher Information: American Thoracic Society, 2021.
Publication Year: 2021
Subject Terms: Leptin, Male, 0301 basic medicine, Vitamin D / analogs & derivatives, obesity, Pulmonary Fibrosis, Calcitriol / metabolism, vitamin D, Inbred C57BL, Inflammation / pathology, Transgenic, Mice, Biomarkers / metabolism, Renin-Angiotensin System / drug effects, Receptors, Renin / blood, Transforming Growth Factor beta1 / metabolism, Insulin, Vitamin D / blood, Lung, transforming growth factor-β1, Cells, Cultured, Methacholine Chloride, 2. Zero hunger, Cultured, Respiratory Hypersensitivity / etiology, Vitamin D Deficiency / blood, 3. Good health, Cytokines, Insulin / metabolism, Obesity / blood, Epithelial-Mesenchymal Transition / drug effects, Epithelial-Mesenchymal Transition, Obesity / complications, Cells, Mice, Transgenic, Pulmonary Fibrosis / blood, Diet, High-Fat, Vitamin D / pharmacology, 03 medical and health sciences, Lung / pathology, Animals, Obesity, Vitamin D Deficiency / etiology, Inflammation, Pulmonary Fibrosis / etiology, Respiratory Hypersensitivity / blood, lung fibrosis, Body Weight, asthma, Glucose Tolerance Test, Leptin / blood, Diet, Body Weight / drug effects, Mice, Inbred C57BL, High-Fat, Cytokines / metabolism, Dietary Supplements, Receptors, Calcitriol, Lung / metabolism, Biomarkers
Description: 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.
Document Type: Article
Language: English
ISSN: 1535-4989
1044-1549
DOI: 10.1165/rcmb.2020-0086oc
Access URL: https://pubmed.ncbi.nlm.nih.gov/33296297
Rights: CC BY NC ND
Accession Number: edsair.doi.dedup.....f2cb84e40d19f76a0020b9d8c94d25ad
Database: OpenAIRE
Description
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.
ISSN:15354989
10441549
DOI:10.1165/rcmb.2020-0086oc