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Lung versus gut exposure to air pollution particles differentially affect metabolic health in mice

Bosch, Angela J T; Rohm, Theresa V; AlAsfoor, Shefaa; Low, Andy J Y; Keller, Lena; Baumann, Zora; Parayil, Neena; Stawiski, Marc; Rachid, Leila; Dervos, Thomas; Mitrovic, Sandra; Meier, Daniel T; Cavelti-Weder, Claudia (2023). Lung versus gut exposure to air pollution particles differentially affect metabolic health in mice. Particle and Fibre Toxicology, 20(1):7.

Abstract

BACKGROUND

Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, the lung has been considered as the main target organ of air pollution. In contrast, the gut has received little scientific attention. Since air pollution particles can reach the gut after mucociliary clearance from the lungs and through contaminated food, our aim was to assess whether exposure deposition of air pollution particles in the lung or the gut drive metabolic dysfunction in mice.

METHODS

To study the effects of gut versus lung exposure, we exposed mice on standard diet to diesel exhaust particles (DEP; NIST 1650b), particulate matter (PM; NIST 1649b) or phosphate-buffered saline by either intratracheal instillation (30 µg 2 days/week) or gavage (12 µg 5 days/week) over at least 3 months (total dose of 60 µg/week for both administration routes, equivalent to a daily inhalation exposure in humans of 160 µg/m$^{3}$ PM$_{2.5}$) and monitored metabolic parameters and tissue changes. Additionally, we tested the impact of the exposure route in a "prestressed" condition (high-fat diet (HFD) and streptozotocin (STZ)).

RESULTS

Mice on standard diet exposed to particulate air pollutants by intratracheal instillation developed lung inflammation. While both lung and gut exposure resulted in increased liver lipids, glucose intolerance and impaired insulin secretion was only observed in mice exposed to particles by gavage. Gavage with DEP created an inflammatory milieu in the gut as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. In contrast, liver and adipose inflammation markers were not increased. Beta-cell secretory capacity was impaired on a functional level, most likely induced by the inflammatory milieu in the gut, and not due to beta-cell loss. The differential metabolic effects of lung and gut exposures were confirmed in a "prestressed" HFD/STZ model.

CONCLUSIONS

We conclude that separate lung and gut exposures to air pollution particles lead to distinct metabolic outcomes in mice. Both exposure routes elevate liver lipids, while gut exposure to particulate air pollutants specifically impairs beta-cell secretory capacity, potentially instigated by an inflammatory milieu in the gut.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Toxicology
Physical Sciences > Health, Toxicology and Mutagenesis
Language:English
Date:9 March 2023
Deposited On:08 Feb 2024 08:53
Last Modified:30 Jan 2025 02:40
Publisher:BioMed Central
ISSN:1743-8977
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12989-023-00518-w
PubMed ID:36895000
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  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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