Abstract
Background: Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrophages (LMs), and 3) the impact of recombinant human adiponectin and a small-molecule APN receptor agonist (AdipoRon) on LMs activation.Material and methods: Human parenchyma explants and LMs were isolated from patients operated for carcinoma. The LMs were cultured with recombinant adiponectin or AdipoRon and stimulated with lipopolysaccharide (10 ng ml−1), poly (I:C) (10 µg ml−1) or interleukin (IL)-4 (10 ng ml−1) for 24 h. Cytokines or adiponectin, released by explants or LMs, were measured using ELISAs. The mRNA levels of AdipoR1 and AdipoR2 were determined using real-time quantitative PCR. AdipoRs expression was also assessed with confocal microscopy.Results: Adiponectin was released by lung explants at a level negatively correlated with the donor’s body mass index. AdipoR1 and AdipoR2 were both expressed in LMs. Adiponectin (3–30 µg ml−1) and AdipoRon (25–50 μM) markedly inhibited the LPS- and poly (I:C)-induced release of Tumor Necrosis Factor-α, IL-6 and chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, CXCL10) and the IL-4-induced release of chemokines (CCL13, CCL17, CCL22) in a concentration-dependent manner. Recombinant adiponectin produced in mammalian cells (lacking low molecular weight isoforms) had no effects on LMs.Conclusion and implications: The low-molecular-weight isoforms of adiponectin and AdipoRon have an anti-inflammatory activity in the lung environment. Targeting adiponectin receptors may constitute a new means of controlling airways inflammation.
Highlights
In a worldwide analysis in 2016, it was estimated that about 671 million adults and 124 million children over the age of four were obese, and that a further 1.3 billion adults and 213 million children over the age of four were overweight (NCD Risk Factor Collaboration (NCD-RisC), 2017).Overweight and obesity are associated with an increased risk of noncommunicable diseases such as diabetes mellitus and cardiovascular disease (GBD 2015 Obesity Collaborators et al, 2017)
Time-course measurements of the APN concentration in explant supernatants highlighted an increase over time, and suggested that APN was released by the tissue (Figure 2A)
APN was not detected in lung macrophage (LM) supernatants - suggesting that these macrophages were not involved in the release of APN by the explants
Summary
Overweight and obesity are associated with an increased risk of noncommunicable diseases such as diabetes mellitus and cardiovascular disease (GBD 2015 Obesity Collaborators et al, 2017). Obesity constitutes a risk factor for respiratory infections such as pneumonia, severe influenza and severe coronavirus disease 2019 (Baik et al, 2000; Morgan et al, 2010; Salvator et al, 2011; Van Kerkhove et al, 2011; Kass and Priya, 2020; Lighter et al, 2020). Circulating levels of APN are lower in obese individuals, and this fall is thought to contribute to obesity-related inflammatory diseases (Arita et al, 1999; Ouchi et al, 2011). Obesity is associated with an elevated risk of severe respiratory infections and inflammatory lung diseases. The objectives were to investigate 1) the production of adiponectin by human lung explants, 2) the expression of the adiponectin receptors AdipoR1 and AdipoR2 by human lung macrophages (LMs), and 3) the impact of recombinant human adiponectin and a small-molecule APN receptor agonist (AdipoRon) on LMs activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
