The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections
The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections
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DOI：
10.1002/oby.22856
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发表时间：
2020-06-10
期刊：
影响因子：
6.9
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
--
作者：
Kruglikov, Ilja L.;Scherer, Philipp E.
由高致病性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）显示出与广泛肺纤维化相关的严重急性呼吸综合征发展引起的高发病率和死亡率。在这个角度来看，我们认为，脂肪细胞和脂肪细胞样细胞，如肺脂肪成纤维细胞，可能发挥重要作用的致病反应，SARS冠状病毒-2。血管紧张素转换酶2（SARS-CoV的功能性受体）在肥胖和糖尿病患者的脂肪细胞中表达上调，这将脂肪组织转变为潜在的靶点和病毒储存库。这可以解释为什么肥胖和糖尿病是COVID-19感染的潜在合并症。与最近建立的脂肪细胞-肌成纤维细胞转变类似，位于肺泡上皮中并与经典脂肪细胞密切相关的肺脂肪成纤维细胞表现出转分化为肌成纤维细胞的能力，所述肌成纤维细胞在肺纤维化中发挥不可或缺的作用。这可能会显著增加肺部对SARS-CoV-2的局部反应的严重程度。为了降低与COVID-19相关的严重程度和死亡率，我们建议探索对噻唑烷二酮（过氧化物酶体增殖物激活受体γ激动剂，众所周知的抗糖尿病药物）的临床反应。噻唑烷二酮类药物能够使脂肪成纤维细胞稳定在其“非活性”状态，防止其转变为肌成纤维细胞，从而减少肺纤维化的发展并刺激其消退。
Coronavirus disease-2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis. In this Perspective, we argue that adipocytes and adipocyte-like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to SARS-CoV-2. Expression of angiotensin-converting enzyme 2 (the functional receptor for SARS-CoV) is upregulated in adipocytes of patients with obesity and diabetes, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID-19 infections. Similar to the recently established adipocyte-myofibroblast transition, pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of pulmonary fibrosis. This may significantly increase the severity of the local response to SARS-CoV-2 in the lung. To reduce the severity and mortality associated with COVID-19, we propose to probe for the clinical response to thiazolidinediones, peroxisome proliferator activated receptor gamma agonists that are well-known antidiabetic drugs. Thiazolidinediones are able to stabilize lipofibroblasts in their "inactive" state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.