Adipose Tissue, Obesity and COVID-19
Thomas Taylor
Adipose Tissue (AT), or more commonly referred to as fat tissue, has been the focus of much research in the last few years after its discovery as a major endocrine organ. It produces a range of endocrine substances known as adipokines 1 which play a significant role in inflammation, metabolic regulation, insulin resistance, immunity and coagulation. 2 AT is thought to be the largest endocrine organ with over 29 different adipokines recognized as of today, such as leptin, adiponectin, TNF-alpha, IL-6, PAI- 1, resistin and adipolin. These chemicals often have either pro-inflammatory properties or anti- inflammatory properties. In individuals with a normal BMI there is a balance between the secretion of pro and anti-inflammatory adipokines. However, in people with a higher BMI there is an upregulation of pro-inflammatory adipokines which contribute to the chronic low-grade state of inflammation and metabolic dysregulation associated with obesity. 3 This state of inflammation is also associated with insulin resistance as well as a pro-thrombotic state initiated by increased platelet reactivity, enhanced coagulation and impaired fibrinolysis, all of which are influenced by the adipose tissue. 4 The combination of a pro-inflammatory, insulin resistant and pro-thrombotic state in obese people increases the risk of developing serious conditions such as type 2 diabetes, cardiovascular diseases (notably atherosclerosis and venous diseases), non-alcoholic fatty liver disease and cancer. 5 Recently, it has been made clear that obesity is a risk factor for COVID-19 because of a more severe state of inflammation in pulmonary AT as well as a higher chance of coagulation. I will consider first the effects of obesity on inflammation, then on coagulation and how these act as risk factors for COVID-19.
Obesity and Inflammation
Obesity, and the inflammation associated with it, can be linked to 2 main processes: (1) the central role of immune cells located within and around AT and (2) the secretion of various adipokines, which through obesity, lead to an upregulation of pro-inflammatory adipokines.
1. The role of immune cells around AT in inflammation Nearly all kinds of immune cells can be found in AT. The most prevalent, macrophages, play a very significant role in inflammation. M1 macrophages ( ‘classically activated’ ) produce and release higher levels of TNF- αand IL -6. This promotes insulin resistance and, through the nature of these cytokines, leads to inflammation. M2 macrophages ( ‘alternatively activated’ ) are responsible for the anti- inflammatory responses of the immune system through the secretion of the anti-inflammatory
1 Smitka et al. 2015 at https://pmr.lf1.cuni.cz/media/pdf/pmr_2015116020087.pdf. 2 Romacho et al., 2014 at https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.12246. 3 Mancuso et al., 2016 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970637/. 4 Vilahur et al., 2017 at https://academic.oup.com/cardiovascres/article/113/9/1046/3791215?login=true. 5 Unamuno et al., 2018 at https://onlinelibrary.wiley.com/doi/full/10.1111/eci.12997.
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