Twenty-five years of research about adipogenic adenoviruses: A systematic review.

Infectious etiology is implicated in chronic diseases such as gastric ulcer or atherosclerosis. However, "infection" is a recent term in the field of obesity. Since the first report in 1982 of obesity due to infection, several microbes have been linked to obesity. Among the adipogenic microbes, avian adenovirus SMAM-1 and human adenovirus Ad36 have been studied most extensively for the past 25 years. Here, we present a systematic review of literature about SMAM-1 and Ad36. Reports from North America, Europe, and Asia reveal strong evidence that Ad36 causes obesity in animals and paradoxically improves glycemic control, and in vitro data provides mechanistic explanation. Considering that experimental Ad36 infection of humans is unlikely, its causative role in human obesity or glycemic control has not been demonstrated unequivocally. Nonetheless, most, but not all, observational studies in children and adults link Ad36 infection to obesity and improvement in glycemic control. The E4orf1 gene of Ad36 was identified as responsible for better glycemic control. Overall, 25 years have considerably advanced knowledge about the role of infection in obesity. Potential translational benefits include the development of vaccines to prevent Ad36-induced obesity and drug development based on the E4orf1 protein to improve glycemic control.