Adipose tissue, obesity, and Covid-19
C-Reactive protein (a marker for inflammation) in the blood plasma. 28 Although there is no clinical evidence for humans, it has been shown in animals that administering adiponectin regularly can reverse obesity as well as diseases related with obesity. 29 Overall, it seems that obesity and an increase in AT mass favour the secretion of pro-inflammatory adipokines. An increase in AT mass, along with adipose necrosis, lead to the polarization of macrophages (M2 to M1) which favour inflammatory cytokines. In terms of adipokines, as seen in numerous studies, the secretion of pro-inflammatory adipokines is upregulated by obesity and, antagonistically, downregulated for anti-inflammatory adipokines.
Obesity and Coagulation
AT dysregulation brought on by obesity also poses complications in terms of coagulation and thrombosis. The main difficulties brought on by obesity are CVD as well as thrombotic complications, which can increase the likelihood of having a myocardial infarction (heart attack), cerebral ischaemia (including stroke) or venous thrombosis or pulmonary embolism (blood clot in the lungs). The pro- thrombotic state brought on by AT has multiple causes. These are; (1) a damaged endothelium (the blood vessel lining) as a result of inflammation, (2) the influence of adipokines on coagulation and (3) the central role of plasminogen activator inhibitor-1 (PAI-1). 1. Effect of a damaged endothelium As mentioned above, obesity leads to a chronic state of low-grade inflammation (as well as oxidative stress-not mentioned here), which are both factors which damage your endothelium. The endothelium plays a key role in modulating the coagulation cascade, platelet aggregation and fibrinolysis (break down of clots) through the secretion of various chemicals. 30 An inflamed endothelium therefore loses much of its anti-thrombotic properties. 2. Adipokines and coagulation A few adipokines are also involved in thrombosis. Due to the dysregulated AT, tissue factor is secreted. Tissue factor is one of the first chemicals which initiates the coagulation cascade. Furthermore, the AT releases less adiponectin. Adiponectin inhibits macrophage expression of tissue factor 31 and lower levels of adiponectin result in more TF release by macrophages. Decreased adiponectin has also been seen to lead to platelet activation. Another adipokine involved in thrombosis is leptin. Increased levels of leptin results in the release of ADP as well as thrombin which, once again, promotes platelet activation. 32 3. The role of PAI-1 PAI-1 (plasminogen activator inhibitor-1) is another adipokine released by AT but this one is directly involved in fibrin deposition. The secretion of PAI-1 leads to fibrin deposition (formation of a clot) by controlling the activities of uPA, tPA (which are fibrinolysis agents) and plasmin. 33 In obese
28 Ouchi et al. (n.6). 29 Tang et al., 2020 at https://onlinelibrary.wiley.com/doi/10.1111/jth.14768. 30 Vilahur et al. (n.4). 31 Okomato et al, 2012 available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580852/. 32 Vilahur et al. (n.4). 33 Ghosh et al, 2013 available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204398/.
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