Advances in Biomedical and Health Sciences (Jan 2022)
Vitamin D attenuates viral-induced inflammation in adipocytes of obese individuals
Abstract
Background: The clinical association between obesity and increased risk of infection is well established; however, the role of adipocytes remains unknown. Adipocytes are important players in the meta-inflammation observed in obese individuals. Moreover, adipocytes are now emerging as potential viral reservoirs for viruses such as SARS-CoV-2, the virus behind the COVID-19 pandemic, due to increased expression of virus receptors [angiotensin converting enzyme-2 (ACE2) and TMPRSS2]. Moreover, obesity has been linked to vitamin D deficiency. We hypothesized that vitamin D supplementation can attenuate the viral-induced inflammation in adipocytes of obese subjects and potentially regulate the expression of viral receptors. Materials and Methods: Adipocytes were differentiated in vitro from subcutaneous human pre-adipocytes obtained from nonobese and obese individuals. Poly(I:C) (10 μg/mL), which binds to toll-like receptor-3 (TLR3), was used to mimic viral infection, in the absence and presence of 100 nM of 1α,25-dihydroxyvitamin D3 for 24 hours. Adipocytes were collected for RNA extraction. qRT-PCR was performed to assess the expression of TLR3, IL-8, IL-6, TNF-α, IFN-β, ACE2, TMPRSS2. Results: Pre-stimulation with Poly(I:C), adipocytes from obese individuals showed higher expression of TLR3, TNF-α, IFN-β, ACE2, and TMPRSS2 highlighting the inflammatory status of obese adipocytes. Following stimulation with Poly(I:C), expression of TLR3, IL-8, TNF-α, and IFN-β were significantly increased in obese adipocytes compared to nonobese. Vitamin D supplementation was able to decrease significantly TLR3, IL-8, and IFN-β expression. Expression of IL-6, ACE2, and TMPRSS2 were increased in both nonobese and obese adipocytes in response to Poly (I:C) with significant effect of vitamin D supplementation on IL-6 and TMPRSS2 expression in obese adipocytes. Conclusion: Vitamin D supplementation provides a potential therapeutic advantage in the viral-induced inflammation seen in adipocytes especially in relation to obesity. Our results also suggest that vitamin D can be used to regulate the expression of receptors and proteases involved in SARS-CoV-2 viral entry.
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