Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular risk factors strictly linked to unhealthy lifestyle, dietary habit and physical inactivity. In male patients, MetS symptoms are often complicated by the onset of hypogonadotropic hypogonadism (HH), with low testosterone (T) and gonadotropin levels. Recent studies have shown the association of lung dysfunction to MetS, but the underlying mechanism remains unclear. Here, we used a well-established rabbit model of high fat diet (HFD)-induced MetS, which recapitulates human phenotype (including HH), to better understand the pathogenesis of lung dysfunction in MetS. In addition, based on previous studies demonstrating the beneficial effects of T treatment in counteracting some MetS symptoms in both pre-clinical [1] and clinical studies [2], we investigated the potential protective action of T on MetS-induced lung alterations. Rabbits fed a HFD for 12 weeks were treated with T during the last 6 weeks and were compared to both untreated HFD and regular diet (RD) rabbits. The assessment of lung function was performed by pressure airway opening (PAO) measurements and evidenced that airway resistance to inflation was significantly increased in HFD rabbits compared to RD. Accordingly, morphological and immunohistochemical analyses showed the occurrence of tissue inflammation, as detected by immunostaining for the macrophagic marker RAM11, and the presence of fibrotic processes, particularly at peribronchiolar level in the lung of HFD animals in comparison to RD. Treatment with T significantly improved not only some metabolic parameters, but also the lung ventilation compared to the HFD group, while it showed a tendency to counteract pro-inflammatory macrophage activation and peribronchiolar fibrosis. In addition, gene expression analysis of the main inflammatory and fibrotic markers confirmed a positive effect of T treatment. In conclusion, our results showed that the HFD-induced MetS model is valid and useful in vivo tool for the study of MetS-related lung dysfunctions, adding new insight into the comprehension of the underlying mechanisms responsible for the morpho-functional changes. Moreover, T treatment could be beneficial in patients with MetS, hypogonadism and pulmonary comorbidities.

Characterization of metabolic syndrome-related morpho-functional changes in the lung and the role of testosterone treatment in an animal model / Giulia Guarnieri, Sandra Filippi, Alessandro Pini, Paolo Comeglio, Ilaria Cellai, Mario Maggi, Linda Vignozzi, Annamaria Morelli. - In: ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY. - ISSN 1122-6714. - ELETTRONICO. - (2022), pp. 0-0.

Characterization of metabolic syndrome-related morpho-functional changes in the lung and the role of testosterone treatment in an animal model.

Giulia Guarnieri;Sandra Filippi;Alessandro Pini;Paolo Comeglio;Ilaria Cellai;Mario Maggi;Linda Vignozzi;Annamaria Morelli
2022

Abstract

Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular risk factors strictly linked to unhealthy lifestyle, dietary habit and physical inactivity. In male patients, MetS symptoms are often complicated by the onset of hypogonadotropic hypogonadism (HH), with low testosterone (T) and gonadotropin levels. Recent studies have shown the association of lung dysfunction to MetS, but the underlying mechanism remains unclear. Here, we used a well-established rabbit model of high fat diet (HFD)-induced MetS, which recapitulates human phenotype (including HH), to better understand the pathogenesis of lung dysfunction in MetS. In addition, based on previous studies demonstrating the beneficial effects of T treatment in counteracting some MetS symptoms in both pre-clinical [1] and clinical studies [2], we investigated the potential protective action of T on MetS-induced lung alterations. Rabbits fed a HFD for 12 weeks were treated with T during the last 6 weeks and were compared to both untreated HFD and regular diet (RD) rabbits. The assessment of lung function was performed by pressure airway opening (PAO) measurements and evidenced that airway resistance to inflation was significantly increased in HFD rabbits compared to RD. Accordingly, morphological and immunohistochemical analyses showed the occurrence of tissue inflammation, as detected by immunostaining for the macrophagic marker RAM11, and the presence of fibrotic processes, particularly at peribronchiolar level in the lung of HFD animals in comparison to RD. Treatment with T significantly improved not only some metabolic parameters, but also the lung ventilation compared to the HFD group, while it showed a tendency to counteract pro-inflammatory macrophage activation and peribronchiolar fibrosis. In addition, gene expression analysis of the main inflammatory and fibrotic markers confirmed a positive effect of T treatment. In conclusion, our results showed that the HFD-induced MetS model is valid and useful in vivo tool for the study of MetS-related lung dysfunctions, adding new insight into the comprehension of the underlying mechanisms responsible for the morpho-functional changes. Moreover, T treatment could be beneficial in patients with MetS, hypogonadism and pulmonary comorbidities.
2022
Giulia Guarnieri, Sandra Filippi, Alessandro Pini, Paolo Comeglio, Ilaria Cellai, Mario Maggi, Linda Vignozzi, Annamaria Morelli
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1391543
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