Esther Guiu-Jurado

Since the emergence of coronavirus disease-19 (COVID-19) in 2019, it has been crucial to investigate the causes of severe cases, particularly the higher rates of hospitalization and mortality in individuals with obesity. Previous findings suggest that adipocytes may play a role in adverse COVID-19 outcomes in people with obesity. The impact of COVID-19 vaccination and infection on adipose tissue (AT) is currently unclear. We therefore analyzed 27 paired biopsies of visceral and subcutaneous AT from donors of the Leipzig Obesity BioBank that have been categorized into three groups (1: no infection/no vaccination; 2: no infection but vaccinated; 3: infected and vaccinated) based on COVID-19 antibodies to spike (indicating vaccination) and/or nucleocapsid proteins. We provide additional insights into the impact of COVID-19 on AT biology through a comprehensive histological transcriptome and serum proteome analysis. This study demonstrates that COVID-19 infection is associated with smaller average adipocyte size. The impact of infection on gene expression was significantly more pronounced in subcutaneous than in visceral AT and mainly due to immune system-related processes. Serum proteome analysis revealed the effects of the infection on circulating adiponectin, interleukin 6 (IL-6), and carbonic anhydrase 5A (CA5A), which are all related to obesity and blood glucose abnormalities.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the PEMT gene, including the waist–hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. PEMT expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, PEMT expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro Pemt knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in PEMT mRNA expression across the three studied tissues. Specifically, vis PEMT mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc PEMT expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT PEMT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of PEMT on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that PEMT plays a role in regulating FD and has implications in metabolic diseases.