Salazar Maria, Ferreira Mariana, Oliveira Sandra Marisa, Saraiva Francisca, Pinho Carlos, Jarnalo Mariana, Correia-Sá Inês, Falcão-Pires Inês, Leite-Moreira Adelino, Neves Delminda, Almeida Henrique, Rodrigues Adriana R, Gouveia Alexandra M
Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto/IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Int J Mol Sci. 2025 Jul 29;26(15):7313. doi: 10.3390/ijms26157313.
Increased body mass index (BMI) and age are associated with COVID-19 severity. SARS-CoV-2 infection occurs through ACE2 binding, with TMPRSS2, ADAM17, and NRP1 facilitating this process. This study describes how adipose tissue (AT) location, BMI, age, and obesity affect these proteins' expression. AT was collected from subcutaneous (abdominal superficial [AS], abdominal deep [AD], thigh [T]) and visceral (epiploon [E]) areas from middle-aged women without obesity (BMI 23.9 kg/m, age 48.3 years). Subcutaneous AT was also obtained from middle-aged women with previous obesity (BMI 24.8 kg/m, previously 41.7 kg/m, age 46.9 years), older women with obesity (BMI 32.3 kg/m, age 70.8 years), and older women without obesity (BMI 23.7 kg/m, age 70.6 years). ACE2, TMPRSS2, ADAM17, and NRP1 expression was evaluated by qPCR and Western blotting. All proteins were more expressed in visceral AT. ACE2, TMPRSS2, and NRP1 positively correlated with BMI in AS and/or E, while NRP1 correlated with age in T. In subcutaneous AT, ACE2 and NRP1 were more influenced by obesity while TMPRSS2 was more age-dependent. In women with previous obesity, ACE2 and NRP1 levels decreased, while TMPRSS2 and ADAM17 remained unchanged. These findings highlight the differential influence of visceral AT, obesity, and age on the expression of SARS-CoV-2 cell entry mediators, potentially contributing to COVID-19 severity.
体重指数（BMI）增加和年龄增长与新冠病毒疾病（COVID-19）的严重程度相关。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）通过与血管紧张素转换酶2（ACE2）结合而发生感染，跨膜丝氨酸蛋白酶2（TMPRSS2）、肿瘤坏死因子α转换酶（ADAM17）和神经纤毛蛋白1（NRP1）促进这一过程。本研究描述了脂肪组织（AT）的位置、BMI、年龄和肥胖如何影响这些蛋白质的表达。从无肥胖的中年女性（BMI 23.9 kg/m²，年龄48.3岁）的皮下（腹部浅层[AS]、腹部深层[AD]、大腿[T]）和内脏（网膜[E]）区域收集AT。还从既往有肥胖史的中年女性（BMI 24.8 kg/m²，既往为41.7 kg/m²，年龄46.9岁）、肥胖老年女性（BMI 32.3 kg/m²，年龄70.8岁）和无肥胖的老年女性（BMI 23.7 kg/m²，年龄70.6岁）获取皮下AT。通过定量聚合酶链反应（qPCR）和蛋白质免疫印迹法评估ACE2、TMPRSS2、ADAM17和NRP1的表达。所有蛋白质在内脏AT中表达更高。ACE2、TMPRSS2和NRP1在AS和/或E中与BMI呈正相关，而NRP1在T中与年龄相关。在皮下AT中，ACE2和NRP1受肥胖影响更大，而TMPRSS2受年龄影响更大。在既往有肥胖史的女性中，ACE2和NRP1水平降低，而TMPRSS2和ADAM17保持不变。这些发现突出了内脏AT、肥胖和年龄对SARS-CoV-2细胞进入介质表达的不同影响，可能导致COVID-19病情加重。
