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腺病毒5型在长期喂养均衡饮食或高脂饮食的动物中会导致肥胖以及不良的代谢、形态和功能变化:一项对仓鼠的研究。

Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters.

作者信息

Montes-Galindo Daniel A, Espiritu-Mojarro Ana C, Melnikov Valery, Moy-López Norma A, Soriano-Hernandez Alejandro D, Galvan-Salazar Hector R, Guzman-Muñiz Jorge, Guzman-Esquivel Jose, Martinez-Fierro Margarita L, Rodriguez-Sanchez Iram P, Paz-Michel Brenda, Zaizar-Fregoso Sergio A, Sanchez-Ramirez Carmen A, Ramirez-Flores Mario, Delgado-Enciso Ivan

机构信息

Department of Molecular Medicine, School of Medicine, University of Colima, Avenue Universidad 333, Colonia Las Víboras, CP 28040, Colima, Mexico.

Department of Research, Cancerology State Institute,Colima State Health Services, 28085, Colima, Mexico.

出版信息

Arch Virol. 2019 Mar;164(3):775-786. doi: 10.1007/s00705-018-04132-6. Epub 2019 Jan 21.

Abstract

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 10 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

摘要

腺病毒5型(Ad-5)感染是急性呼吸道感染的常见病因,也是基因治疗中使用的主要载体。关于Ad-5与肥胖之间关系的研究较少。在本研究中,我们评估了Ad-5感染对喂食均衡饮食(BD)或高脂饮食(HFD)的金黄(叙利亚)仓鼠的慢性影响。单次接种Ad-5(1×10 pfu)后,每周测量动物的体重。进行了中期(22周)血清生化分析以及长期(44周)肝脏形态、肥胖程度和运动功能(运动速度)评估。在喂食BD的动物中,腺病毒感染导致了高血糖和高血脂。长期来看,与未接种的动物相比,附睾脂肪垫增加了57%,体重增加了30%。此外,还观察到了与非酒精性脂肪性肝病(NAFLD)相关的形态学变化。喂食HFD的动物有类似但更严重的变化。此外,仓鼠出现了肥胖悖论:在研究结束时,形态和功能变化最大(运动速度显著降低)的动物体重最低。尽管从长期来看,高脂饮食似乎比单独的腺病毒感染更具有害性,但感染可能会增加高脂饮食个体的有害影响严重程度。需要进行流行病学研究来评估腺病毒作为慢性肝脏和心血管疾病前驱因素的影响,包括基因治疗的慢性影响。

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