Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France.
Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France.
Med Hypotheses. 2020 Nov;144:110023. doi: 10.1016/j.mehy.2020.110023. Epub 2020 Jun 23.
Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPs (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage.
一致的观察报告表明，超重且伴有心血管因素的男性感染 SARS-CoV-2 的严重程度更高。由于内脏脂肪具有强烈的免疫活性，与代谢综合征有关，并处于肠道、全身循环和肺部之间的交叉点，我们假设它在 SARS-CoV-2 感染的严重形式中起主要作用。SARS-CoV2 具有感染呼吸道和肠道上皮细胞的能力。多种因素可能会增加肠道通透性，包括 SARS-CoV2 对肠细胞的直接损伤、全身性炎症反应综合征（SIRS）和 SARS-CoV2 相关内皮功能障碍导致的上皮缺血。这种通透性的增加进一步导致微生物成分（如 MAMPs）的易位，触发肠系膜脂肪中 TLR 表达细胞（主要是巨噬细胞和脂肪细胞）的炎症免疫反应。肠系膜脂肪产生的促炎细胞因子通过肠系膜淋巴引流介导全身炎症，并通过肠内淋巴引流加重急性呼吸窘迫综合征（ARDS）。
