Diet-Induced Obesity and NASH Impair Disease Recovery in SARS-CoV-2-Infected Golden Hamsters.
Diet-Induced Obesity and NASH Impair Disease Recovery in SARS-CoV-2-Infected Golden Hamsters.
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DOI：
10.3390/v14092067
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发表时间：
2022-09-17
期刊：
影响因子：
--
通讯作者：
Trottein F
中科院分区：
文献类型：
--
作者：
Briand F;Sencio V;Robil C;Heumel S;Deruyter L;Machelart A;Barthelemy J;Bogard G;Hoffmann E;Infanti F;Domenig O;Chabrat A;Richard V;Prévot V;Nogueiras R;Wolowczuk I;Pinet F;Sulpice T;Trottein F
患有非酒精性脂肪性肝炎（NASH）的肥胖患者容易患上严重形式的COVID-19。迫切需要新的治疗方法来降低COVID-19在这一脆弱人群中的严重程度。为了更好地复制人类背景，我们在金黄仓鼠中建立了一个饮食诱导的肥胖症与血脂异常和NASH相关的模型（已知是COVID-19的相关临床前模型）。20周的自由选择饮食诱导金黄仓鼠肥胖、血脂异常和NASH（肝脏炎症和纤维化）。肥胖的NASH仓鼠具有较高的血液和肺部炎性细胞因子水平。在SARS-CoV-2感染的早期阶段，瘦仓鼠和肥胖NASH仓鼠的肺部病毒载量和炎症水平相似。然而，肥胖NASH仓鼠显示出更差的恢复（即，感染后10天（DPI）肺部炎症消退较少，DPI 25时体重恢复较低）。肥胖NASH仓鼠在dpi 25时也表现出较高水平的肺纤维化。与瘦动物不同，感染SARS-CoV-2的肥胖NASH仓鼠表现出长期的血脂异常和全身炎症。相对于瘦对照，肥胖NASH仓鼠具有较低的血清血管紧张素转换酶2活性水平和较高的血清血管紧张素II-已知有利于炎症和纤维化的组分水平。尽管SARS-CoV-2感染导致早期体重减轻和体重恢复不完全，但肥胖NASH仓鼠在dpi 25时显示出持续的肝脏脂肪变性、炎症、肝细胞气球样变和显著的肝纤维化。我们得出结论，饮食诱导的肥胖和NASH损害SARS-CoV-2感染仓鼠的疾病恢复。该模型可能有助于表征COVID-19的病理生理机制，并评估在肥胖NASH患者中观察到的严重形式COVID-19的治疗效果。
Obese patients with non-alcoholic steatohepatitis (NASH) are prone to severe forms of COVID-19. There is an urgent need for new treatments that lower the severity of COVID-19 in this vulnerable population. To better replicate the human context, we set up a diet-induced model of obesity associated with dyslipidemia and NASH in the golden hamster (known to be a relevant preclinical model of COVID-19). A 20-week, free-choice diet induces obesity, dyslipidemia, and NASH (liver inflammation and fibrosis) in golden hamsters. Obese NASH hamsters have higher blood and pulmonary levels of inflammatory cytokines. In the early stages of a SARS-CoV-2 infection, the lung viral load and inflammation levels were similar in lean hamsters and obese NASH hamsters. However, obese NASH hamsters showed worse recovery (i.e., less resolution of lung inflammation 10 days post-infection (dpi) and lower body weight recovery on dpi 25). Obese NASH hamsters also exhibited higher levels of pulmonary fibrosis on dpi 25. Unlike lean animals, obese NASH hamsters infected with SARS-CoV-2 presented long-lasting dyslipidemia and systemic inflammation. Relative to lean controls, obese NASH hamsters had lower serum levels of angiotensin-converting enzyme 2 activity and higher serum levels of angiotensin II—a component known to favor inflammation and fibrosis. Even though the SARS-CoV-2 infection resulted in early weight loss and incomplete body weight recovery, obese NASH hamsters showed sustained liver steatosis, inflammation, hepatocyte ballooning, and marked liver fibrosis on dpi 25. We conclude that diet-induced obesity and NASH impair disease recovery in SARS-CoV-2-infected hamsters. This model might be of value for characterizing the pathophysiologic mechanisms of COVID-19 and evaluating the efficacy of treatments for the severe forms of COVID-19 observed in obese patients with NASH.
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4.5
作者：
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影响因子：
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