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
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 × 107 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.
The present study was completed using equipment resources obtained through Grant no. 270485 from the 2016-INFRAESTRUCTURA-CONACYT (author ADSH) and Grant no. 272792 from the 2016-FOSISS-CONACYT (author IDE).
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Disclosure of potential conflicts of interest
Esteripharma Mexico SA de CV provided support in the form of salaries for author BPM but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. That commercial affiliation does not alter our adherence to the “Archives of Virology” policies on sharing data and materials. The others authors declare that they have no conflict of interest.
The trials complied with the national and international legal and ethical requirements applicable to pre-clinical research. The experimental protocols were approved by the Research Ethics Committee of the School of Medicine of the University of Colima, Mexico (Protocol Number: 14-016). The animals were handled according to institutional guidelines, the Mexican official norm regulating laboratory animal use (NOM-062-ZOO-1999), and the guide for the care and use of laboratory animals issued by the National Academy of Sciences of the United States of America (2011). All animals were euthanized according to the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals: 2013 Edition.
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