De Sibio Maria Teresa, Vieira Ester Mariane, Da Rocha Paula Barreto, De Oliveira Miriane, Olímpio Regiane Marques Castro, Peghinelli Vinícius Vigliazzi, Mathias Lucas Solla, Tilli Helena Paim, Gonçalves Bianca Mariani, Deprá Igor, Bravin Maria Beatriz, Lourenço Mariana Menezes, Luca Giovanna Bonatto, de Souza Marino Matheus, Kossooski Pedro Henrique Soares, Corrêa Camila Renata, Sakalem Marna Eliana, Pulido Cormarie Fernández, Nogueira Célia Regina
Endocr Connect. 2025 Aug 7;14(8). doi: 10.1530/EC-25-0046. Print 2025 Aug 1.
COVID-19 is associated with an inflammatory pathophysiology and, when associated with chronic diseases, can trigger severe infection and increase death risk. Irisin, a hormone produced by skeletal muscle during physical activity, has demonstrated therapeutic effects against metabolic disorders and exhibits anti-inflammatory and antioxidant effects. There is great interest in investigating irisin's influence on the interaction between SARS-CoV-2 and host cells. The aim of the present study is to investigate the role of irisin in viral infection in monolayers (2D) or three-dimensional (3D) cell cultures of human subcutaneous adipocytes infected with a SARS-CoV-2 pseudovirus (PV).
Preadipocytes were cultured to maturity in 2D or 3D conditions and divided into four groups: Group 1: adipocytes with no treatment; Group 2: adipocytes optimized for angiotensin-converting enzyme 2 (ACE2) expression; Group 3: adipocytes optimized for ACE2 expression, and then exposed to SARS-CoV-2 pseudovirus (ACE2+PV); and Group 4: adipocytes treated with irisin 20 nM for 24 h, optimized for ACE2 expression and exposed to PV (ACE2+I+PV). Fluorescence levels of SARS-CoV-2 PV and ACE2 were measured to investigate cell infection; lactate dehydrogenase (LDH) activity to investigate cytotoxicity; and malondialdehyde (MDA) and protein carbonylation to assess oxidative stress levels.
Irisin significantly reduced viral particle (PV) capture in 2D and 3D conditions. In addition, irisin decreased LDH release, MDA, and protein carbonylation levels, both in 2D and 3D conditions.
The results indicate irisin as a promising therapeutic target against COVID-19 pathophysiology by reducing viral entry into adipose cells as well as reducing cytotoxicity and oxidative stress indicators.
新型冠状病毒肺炎（COVID-19）与炎症病理生理学相关，当与慢性疾病相关时，可引发严重感染并增加死亡风险。鸢尾素是骨骼肌在体育活动时产生的一种激素，已证明其对代谢紊乱具有治疗作用，并具有抗炎和抗氧化作用。研究鸢尾素对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与宿主细胞相互作用的影响具有重要意义。本研究的目的是探讨鸢尾素在感染SARS-CoV-2假病毒（PV）的人皮下脂肪细胞单层（二维，2D）或三维（3D）细胞培养物中的病毒感染中的作用。
将前脂肪细胞在2D或3D条件下培养至成熟，并分为四组：第1组：未处理的脂肪细胞；第2组：针对血管紧张素转换酶2（ACE2）表达进行优化的脂肪细胞；第3组：针对ACE2表达进行优化，然后暴露于SARS-CoV-2假病毒的脂肪细胞（ACE2 + PV）；第4组：用20 nM鸢尾素处理24小时，针对ACE-2表达进行优化并暴露于PV的脂肪细胞（ACE2 + I + PV）。测量SARS-CoV-2 PV和ACE2的荧光水平以研究细胞感染；测量乳酸脱氢酶（LDH）活性以研究细胞毒性；测量丙二醛（MDA）和蛋白质羰基化以评估氧化应激水平。
鸢尾素在2D和3D条件下均显著降低了病毒颗粒（PV）的捕获。此外，鸢尾素在2D和3D条件下均降低了LDH释放、MDA和蛋白质羰基化水平。
结果表明，鸢尾素有望成为对抗COVID-19病理生理学的治疗靶点，它可减少病毒进入脂肪细胞，同时降低细胞毒性和氧化应激指标。
