It is a given that as soon as a child starts to attend a pre-school creche, they will come home with sniffles and occasionally a sore eye from conjunctivitis. The root cause is an adenovirus which will be readily spread as droplets in expired air and, because the adenovirus is not easily disinfected, it is readily spread by shared surfaces. Sound familiar? There is one particular adenovirus that attracts the attention of those in the obesity field that are capable of thinking outside the box, a rare breed, let it be said. Back in 1982, veterinary researchers in Mumbai noted that when chickens were injected with canine distemper virus, they became very fat. Shortly afterwards, other viruses were shown to be drivers of obesity such as the virus that causes scrapie in sheep or an avian adenovirus known as SMAM-1 . Studies then turned to humans to explore if there might be link between excess body weight and some virus and the candidate virus that has emerged is the adenovirus 36 or Adv 36. The first study (n= 502) to show this was in 2002, with an infection prevalence of 11% in those of normal weight and 30% among the obese population . Since then, an additional 36 studies have examined the role of Adv 36 in human obesity and a recent systematic review of the literature in this field has concluded that: ”Strong evidence suggested a possible association between viral infection and obesity” . In general, this blogger dislikes association studies but in this instance, it is the best we can do since it would be unethical to experimentally infect a human with Adv 36. There are, however, data other than association data to help us understand the role of Adv 36 in obesity. That very first study of Adv 36 in human obesity also included 26 pairs of twins (20 identical and 6 non-identical). What was important in this study was that infection was discordant among the twins, that is, one twin was positive and one was negative for infectivity. The infected twins had a higher body mass index (26.1 v.24.5 kg/m2) and a higher overall % body fat (29.6 v. 27.5 as measured using hydrondensitometry or dual emission X-ray absorptiometry).
The experimental data from animals consistently shows among chickens, rats and monkeys that experimental infection with Adv 36 causes obesity. All show a significant rise in adiposity and all show no change whatsoever in energy intake. Perhaps the most interesting study was at the Wisconsin Primate Research Centre where blood samples were taken from Rhesus monkeys every 6 months for 90 months. The samples were stored frozen and accessed to test for Adv 36 infection . This study therefore relied on natural infection rather than experimental infection. Only those monkeys that remained seronegative for Adv 36 over an initial 18 moths were included in the study. During this Adv 36-free period, bodyweight changed very little (0.3% or 0.04 kg). However, once they became naturally infected, body weight increased by 15% or 1.7 kg.
Both the discordant twin study and the longitudinal monkey study of natural infection provide compelling evidence for a possible role of Adv 36 in human obesity. The stand-out discovery is that neither in experimentally infected or naturally infected animals did energy intake change. So how does Adv 36 cause increased fat mass if it has zero effect on energy intake? It does this by stimulating stem cells in adipose tissue to differentiate into adipocytes thus creating more fat cells (hyperplasia) . The virus also causes a shift in biochemical regulation of fat and glucose metabolism such that the fat cells get fatter (hypertrophy). All of this centres around a protein enzyme, AMP kinase, which is a central regulator in intracellular levels of energy stores.
So where does this leave us? The answer is, unchanged. Genes load the gun but the environment pulls the trigger so while obesity is highly heritable (multiple twin studies,) it is the obesogenic environment that matters: cheap, palatable and energy dense foods and a totally sedentary environment. Nobody would suggest that viral infection is the cause of obesity but it deserves more than its current orphaned role.
