Adipose tissue, obesity, and Covid-19
cytokine IL-10. 6 They also induce a downregulation of pro-inflammatory cytokines. It is thought that M1 macrophages fight infections and pathogens whereas M2 macrophages play a big role in repair. 7 Obesity leads to a shift in balance from M2 to M1 macrophages in AT and also results in an increased accumulation of M1 macrophages in AT. 8 As a consequence of metabolically dysfunctional AT from obesity, there will be higher levels of adipocyte necrosis, which leaves M1 macrophages in a crown-like structure around the dead tissue. Lymphocytes have also been identified in AT and these contribute to local and systemic inflammation through the secretion of various cytokines. Lastly, T-cell subsets (e.g. CD4+ Th cells – T helper cells) are also prevalent in AT. They are also involved in local inflammation but more crucially influence the polarization of macrophages fromM2 to M1. 9 2. The role of adipokines in inflammation In general, the adipokines can be split into pro or anti-inflammatory cytokines, each having a number of roles within the body. The most well-known adipokine, leptin, was discovered in 1994 and many researchers believed it could be key to dealing with obesity because of its role in appetite regulation. Leptin is a satiety hormone which, when secreted, inhibits hunger through leptin receptors in the hypothalamus and central nervous system. Rather counter intuitively, leptin levels positively correlate with body fat in obese individuals. 10 This has led to the idea of leptin resistance as a result of over secretion. Leptin is released after a meal and effectively makes you feel satiated. Due to more eating, obese individuals will secrete more leptin until they develop leptin resistance. This in turn makes it even harder for obese individuals to no longer feel hungry, contributing to an even greater increase in BMI. Leptin is a pro-inflammatory cytokine and the release of leptin also increases the production of several pro-inflammatory cytokines from monocytes, such as IL-6 and TNF-a. Finally, Leptin also polarizes T-Cells to a Th1 phenotype instead of a Th2, which is another cause of inflammation. 11 Resistin is another adipokine that it is only released by macrophages and monocytes in adipose tissue and not adipocytes. Resistin influences po-inflammatory properties by stimulating the secretion of TNF-a and IL-6 from AT bound macrophages and monocytes. 12 An experiment done by Qatani et al suggested that the inflammatory state promoted by resistin was linked with developing insulin resistance. Nonetheless, this experiment was done on mice and it has been found that we only share 59% of our amino acid base sequence for resistin, 13 which suggests the role of resistin in mice and human may be very different. Piestrzeniewicz et al (2008) 14 reported that resistin levels were higher in obese individuals. Furthermore, high levels of resistin are predictive of developing cardiovascular disease, such as atherosclerosis. 15
6 Smitka et al. (n.1); Ouchi et al., 2011 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518031/. 7 Mancuso et al. (n.3). 8 Ouchi et al. (n.6). 9 Mancuso et al. (n.3). 10 Mendoza-Nunez et al., 2002 at https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2002.34. 11 Ouchi et al. (n.6). 12 Ibid. 13 Kyu Park et al., 2017 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339472/. 14 Piestrzeniewicz et al., 2008 at https://www.metabolismjournal.com/article/S0026-0495(07)00403-9/fulltext. 15 Reilly et al., 2005 at https://www.ahajournals.org/doi/10.1161/01.CIR.0000155620.10387.43?url_ver=Z39.88- 2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&.
65
Made with FlippingBook Digital Publishing Software