Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

Dinger, Katharina; Kasper, Philipp; Hucklenbruch‐Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae‐Gartz, Inga; Koningsbruggen-Rietschel, Silke van; Plank, Christian; Dötsch, Jörg; Alcázar, Miguel A. Alejandre

doi:10.1038/srep24168

Cited by 30 publications

(46 citation statements)

References 58 publications

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“…Our results are comparable to a recent model of murine pre and postnatal hyperalimentation showing increased AHR without alteration in bronchial structure that may be due in part increased T h 17 cells (Dinger et al. ).…”

Section: Discussionsupporting

confidence: 89%

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Maternal high‐fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring

MacDonald

Moran

Scherman

et al. 2017

Physiological Reports

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Maternal obesity prior to and during pregnancy has been associated with an increased incidence of childhood asthma. As diets rich in saturated fat are linked to obesity and inflammation, we created a murine model to investigate the effect of maternal high‐fat diet (HFD) on adult offspring airway hyperreactivity (AHR), a cardinal feature of asthma. Balb/cByJ dams were fed a HFD (60% fat Calories) or normal‐fat diet (NFD) (10% fat Calories) from 8 weeks prior to first breeding through their pregnancies. Pups were weaned to either a HFD or NFD (at 4 weeks of age). AHR was measured in the 10‐week‐old offspring following inhaled methacholine challenge by end‐inflation technique. Bronchial alveolar lavage fluid (BALF) was analyzed for cell count, total protein, and IL‐6. Offspring of HFD dams weaned to NFD had increased AHR compared to offspring of NFD dams weaned to NFD. Offspring of HFD dams that remained on HFDs had increased AHR compared to offspring of NFD dams weaned to HFDs. Offspring of HFD dams had higher BALF cell counts, higher neutrophil percentage, greater total protein, and IL‐6 in the BALF. These results demonstrate that a maternal diet high in saturated fat through pregnancy and lactation plays a key role in programming adult offspring AHR.

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Section: Discussionsupporting

confidence: 89%

“…Our results show increased AHR in HFD offspring that continued on HFD compared to offspring fed HFD at weaning. Our results are comparable to a recent model of murine pre and postnatal hyperalimentation showing increased AHR without alteration in bronchial structure that may be due in part increased T h 17 cells (Dinger et al 2016).…”

Section: Discussionsupporting

confidence: 88%

Maternal high‐fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring

MacDonald

Moran

Scherman

et al. 2017

Physiological Reports

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“…Previous studies related to obesity‐associated asthma suggest that AHR develops as a result of adipokine‐induced dysregulation of airway contractility, lung fibrosis, changes in collagen and elastin expression, and non‐Th2 inflammation . In contrast, we found that short‐term HFD feeding–induced metabolic alterations in OVA‐driven experimental allergic asthma are associated with protection from AHR development, pulmonary inflammation, altered DC activity and decreased Th1/Th17 differentiation.…”

Section: Discussioncontrasting

confidence: 67%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

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“…In accordance with those findings, it was also described that non-allergen-sensitized mice and rats born to mothers exposed to HFD during pregnancy and lactation spontaneously develop lower respiratory system compliance and higher respiratory system resistance [18,19]. Similar data were found in adult non-allergen-sensitized offspring of mice breastfed by dams consuming HFD [20].…”

Section: Introductionsupporting

confidence: 79%

Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring

et al. 2019

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It was previously demonstrated that non-allergen-sensitized rodents born to mothers exposed to a high-fat diet (HFD) spontaneously develop lower respiratory compliance and higher respiratory resistance. In the present study, we sought to determine if mice born to mothers consuming HFD would exhibit changes in inflammatory response and lung remodeling when subjected to ovalbumin (OVA) sensitization/challenge in adult life. Mice born to dams consuming either HFD or standard chow had increased bronchoalveolar lavage (BAL) levels of IL-1β, IL-4, IL-5, IL-10, IL-13, TNF-α and TGF-β1 after challenge with OVA. IL-4, IL-13, TNF-α and TGF-β1 levels were further increased in the offspring of HFD-fed mothers. Mice born to obese dams also had exacerbated values of leukocyte infiltration in lung parenchyma, eosinophil and neutrophil counts in BAL, mucus overproduction and collagen deposition. The programming induced by maternal obesity was accompanied by increased expression of miR-155 in peripheral-blood mononuclear cells and reduced miR-133b in trachea and lung tissue in adult life. Altogether, the present data support the unprecedented notion that the progeny of obese mice display exacerbated responses to sensitization/challenge with OVA, leading to the intensification of the morphological changes of lung remodeling. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression. 13 of 23 HFD/OVA mice (respectively, 172% and 177% higher than in SC/SHAM and HFD/SHAM; p = 0.006 and p < 0.0001). In contrast to IL-1β, the level of TNF-α in BAL of HFD/OVA was higher than in those of SC/OVA (86% higher; p = 0.0008) (p = 0.01 for interaction) (Figure 6b).

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Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

Cited by 30 publications

References 58 publications

Maternal high‐fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring

Maternal high‐fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring

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