What we know and what we need to know about adenovirus 36-induced obesity

Background: Many internal and external factors are related to obesity. Pathogens that can induce obesity are the most interesting external factors. While the relationship between pathogenic human intestinal microbiota and obesity has been extensively studied, viruses have received relatively little attention. Among the human obesity-related viruses, adenovirus 36 (Ad36) is most commonly associated with obesity. Methods: A literature search was conducted using the articles in the PubMed database published from April 1982 to April 2019. The following main keywords were used: (‘adenovirus 36’) and (‘obesity’) and (‘cellular mechanism’ or ‘genetic factor’ or ‘immune response’ or ‘inflammation’). Results: In this review, we have discussed the known facts and what requires to be understood regarding Ad36-induced obesity. In particular, we have summarized the cellular mechanism of Ad36-induced obesity, as well as the genetic and immunological factors affected by Ad36 infection. Ad36 infection increases adipogenesis in animals and humans. Ad36-induced inflammation contributes to angiogenesis in adipose tissues, thereby maintaining proper glycemic control and metabolic robustness. The E4orf1 protein derived from Ad36 is responsible for increasing glucose uptake due to the translocation of GLUT4 via the Ras-PI3K pathway, which is involved in ‘distal’ insulin signaling. Conclusions: We expect that this review will assist in guiding future investigations regarding Ad36-induced obesity. (1) Identification of the direct and indirect factors affecting Ad36-induced obesity and understanding their mechanism of action and (2) utilization of the Ad36-induced improvement in glycemic control for clinical applications, with efforts toward developing E4orf1-based drugs.