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Nikhil Prasad  Fact checked by:Thailand Medical News Team Feb 09, 2024  3 weeks, 4 hours, 19 minutes ago

BREAKING! SARS-CoV-2 Alters The Phenotype And Gene Expression Of Adipocytes Which Can Cause Various Long Term Issues!

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BREAKING! SARS-CoV-2 Alters The Phenotype And Gene Expression Of Adipocytes Which Can Cause Various Long Term Issues!
Nikhil Prasad  Fact checked by:Thailand Medical News Team Feb 09, 2024  3 weeks, 4 hours, 19 minutes ago
COVID-19 News: The COVID-19 pandemic caused by the SARS-CoV-2 virus has presented unprecedented challenges globally, with severe outcomes often associated with comorbidities such as obesity. Understanding the complex interplay between SARS-CoV-2 and adipocytes, the cells primarily responsible for storing fat, is critical for comprehending the disease's progression and long-term implications. Researchers from the University of Pisa in Italy, in collaboration with various institutions, have conducted a groundbreaking study that is covered in this COVID-19 News report, employing an in vitro model to investigate how SARS-CoV-2 affects adipocytes, shedding light on potential long-term consequences.


Phenotypes of SGBS pre-adipocytes and adipocytes, as revealed by confocal microscopy. (A,B) One SGBS pre-adipocyte (A) and one SGBS adipocyte (B) stained by Hoechst and Oil red, and confocally imaged at the medial plane by collecting fluorescence in the blue and far-red channels. (C,D) One SGBS pre-adipocyte (C) and one SGBS adipocyte (D) immunostained for ACE2 (primary Ab: rabbit antiACE2, secondary Ab: αr488) confocally imaged at the membrane plane by collecting fluorescence in the green channel. Fluorescence intensity was coded by a pseudo-color FireHot scale to pinpoint the strong difference in expression levels between the two cell types. In all cases, the cell’s contours were highlighted by a white line. Scale bar: 10 μm.

The Connection Between COVID-19 and Obesity
Obesity, a global health issue closely linked to poverty and socioeconomic disadvantage, has emerged as an independent risk factor for severe and lethal forms of COVID-19. Epidemiological evidence underscores the association between excess fat mass and an increased risk of severe COVID-19 disease. Individuals with obesity often exhibit a spectrum of other conditions typical of the metabolic syndrome, such as hypertension and type 2 diabetes, which further exacerbate the risk of severe COVID-19. Moreover, obesity is characterized by a chronic state of low-grade systemic inflammation, which primes the onset of comorbidities associated with obesity. Notably, adipose tissue, particularly white adipose tissue (WAT), has been identified as a target for SARS-CoV-2 infection and a potential reservoir for prolonged viral shedding, suggesting a possible contribution to the long-term effects of COVID-19.
 
Adipocytes and ACE2 Expression
Adipocytes express the membrane-bound glycoprotein angiotensin-converting enzyme 2 (ACE2), which serves as a critical entry point for the virus. The study utilizes the human Simpson-Golabi-Behmel syndrome (SGBS) cell line, which closely mimics primary human adipocytes, to investigate the infectivity of SARS-CoV-2 in adipocytes. Results demonstrate that SGBS adipocytes expressing ACE2 are susceptible to SARS-CoV-2 infection, as evidenced by the detection of viral particles, nucleocapsid protein, and positive immunostaining for the spike protein. These findings reveal substantial morphological and functional changes in infected adipocytes, highlighting the virus's impact on adipocyte biology.

Effects of SARS-CoV-2 on Adipocyte Morphology an d Gene Expression
Differentiated SGBS adipocytes exhibit susceptibility to SARS-CoV-2 infection, leading to remarkable changes in morphology and gene expression. Infected adipocytes display an increase in the size of lipid droplets, which are the main reservoirs of triglycerides within adipocytes. Additionally, gene expression analysis reveals an upregulation of inflammatory genes and increased oxidative stress in infected adipocytes. Notably, there is a concomitant reduction in the expression of genes associated with adipocyte function, such as those involved in lipid synthesis and metabolism. Furthermore, exogenous expression of the spike protein in SGBS adipocytes results in an enlargement of lipid droplets, suggesting that the spike protein alone is sufficient to induce morphological changes observed during SARS-CoV-2 infection.
 
Exploring the Role of Spike Protein
The spike protein of SARS-CoV-2 plays a crucial role in mediating viral entry into host cells and membrane fusion. To investigate the specific role of the spike protein in inducing morphological changes in adipocytes, the study conducted transient transfections of SGBS cells with spike protein-encoding plasmids during adipogenic conversion. Remarkably, cells expressing the spike protein exhibited larger lipid droplets compared to control cells, supporting the hypothesis that the spike protein mediates the fusion of lipid vacuoles, contributing to the observed morphological changes in infected adipocytes.
 
Long-Term Implications and Future Directions
The study's findings provide valuable insights into the complex interaction between SARS-CoV-2 and adipocytes, uncovering substantial transformations in adipocyte function during COVID-19. The observed inflammatory response, coupled with impaired adipocyte function and triglyceride storage capacity, suggests potential long-term consequences of SARS-CoV-2 infection on adipose tissue. Certain endocrine functions could also be disrupted as a result of the alterations to the adipocytes.
 
Furthermore, the study highlights the importance of understanding the virus's impact not only in the acute phase but also in predicting potential long-term effects on metabolic health and immune response. Future research should focus on elucidating the mechanisms underlying these observed changes and exploring potential therapeutic interventions targeting adipocyte function in COVID-19 patients.
 
Conclusion
In conclusion, the groundbreaking research conducted by the University of Pisa and collaborating institutions sheds light on the profound alterations induced by SARS-CoV-2 in adipocytes. By employing an in vitro model, the study provides crucial insights into the virus's impact on adipocyte biology, revealing significant morphological and functional changes in infected cells. As the world continues to grapple with the COVID-19 pandemic, this research underscores the importance of understanding the complex interplay between the virus and adipose tissue, paving the way for future studies aimed at mitigating the long-term consequences of SARS-CoV-2 infection on metabolic health and immune function.
 
The study finings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/4/2086
 
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