TGF-β: The missing link in obesity-associated airway diseases?

Abstract

Obesity is emerging as a global public health epidemic. The co-morbidities associated with obesity significantly contribute to reduced quality of life, mortality, and global healthcare burden. Compared to other asthma comorbidities, obesity prominently engenders susceptibility to inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), contributes to greater disease severity and evokes insensitivity to current therapies. Unlike in other metabolic diseases associated with obesity, the mechanistic link between obesity and airway diseases is only poorly defined. Transforming growth factor-β (TGF-β) is a pleiotropic inflammatory cytokine belonging to a family of growth factors with pivotal roles in asthma. In this review, we summarize the role of TGF-β in major obesity-associated co-morbidities to shed light on mechanisms of the diseases. Literature evidence shows that TGF-β mechanistically links many co-morbidities with obesity through its profibrotic, remodeling, and proinflammatory functions. We posit that TGF-β plays a similar mechanistic role in obesity-associated inflammatory airway diseases such as asthma and COPD. Concerning the role of TGF-β on metabolic effects of obesity, we posit that TGF-β has a similar mechanistic role in obesity-associated inflammatory airway diseases in interplay with different comorbidities such as hypertension, metabolic diseases like type 2 diabetes, and cardiomyopathies. Future studies in TGF-β-dependent mechanisms in obesity-associated inflammatory airway diseases will advance our understanding of obesity-induced asthma and help find novel therapeutic targets for prevention and treatment.

TGF-β, IL-1β, IL-6 levels and TGF-β/Smad pathway reactivity regulate the link between allergic diseases, cancer risk, and metabolic dysregulations

“…It is noteworthy that the involvement of TGF-β in metabolic dysregulations has been previously documented ( 165 ). Nevertheless, to the author ’ s knowledge, this is the first piece of work that establishes a connection between TGF-β/Smad pathway, IL-1β and IL-6 levels, metabolic pathways, the type of allergy, metabolic dysregulations, and the risk of cancer within a unified framework.…”

Associations of obesity with chronic inflammatory airway diseases and mortality in adults: a population-based investigation

“…CIAD (including COPD, asthma and chronic bronchitis) are closely related to inflammation, while adipokine that promotes the occurrence and development of inflammation mainly originates from adipose tissue. Therefore, as a low-grade systemic inflammation driven by phenotypic changes in adipose tissue-related macrophages, obesity is very likely to cause inflammatory airway diseases such as asthma and COPD [ 27 , 28 ]. On the other hand, patients with obesity have an increase in peripheral blood leukocytes, which may lead to increased inflammation and the production of more pro-inflammatory mediators [ 29 ].…”

Management of BMI Is a Potential New Approach for the Prevention of Idiopathic Pulmonary Fibrosis

“…Patients with IPF have a higher level of transforming growth factor-β (TGF-β) in bronchoalveolar lavage than normal controls. TGF-β is one of the most strong regulators of connective tissue synthesis and is significantly increased in patients with obesity ( Woo et al, 2021 ). Moreover, several other obesity-related inflammatory factors, including IL-17, leptin, adiponectin, NLRP3 inflammasome, and TLR-4 have been implicated in the pathogenesis of lung disease.…”