Infectobesity: the bugs that make you fat
We’re getting fatter. The World Health Organization recently declared that there is an epidemic of obesity (having too much body fat). In the past 20 years, the prevalence of obesity has increased by 30% in the USA. In the UK it is estimated that one in five men and a quarter of women are obese and that as many as 30,000 people die prematurely every year from obesity-related conditions. Experts believe that obesity is responsible for even more ill health than smoking. Being significantly overweight is linked to a wide range of health problems, including: heart disease, high blood pressure, arthritis, diabetes, gallstones, some cancers (e.g. breast, prostate), stress, anxiety, and depression. Wouldn’t it be nice if it wasn’t all our fault, and if meaning to go to the gym was as effective as a long workout. Wouldn’t if be nice to have an excuse for being slightly tubby. In the last two decades, 10 adipogenic (fat causing) pathogens have been reported: these include human and nonhuman viruses, prions, bacteria, and gut microflora. Some of these pathogens are statistically associated with human obesity, but their causative role has not been established. If relevant to humans, “Infectobesity” would be a relatively novel, yet extremely significant medical concept. A new perspective about the infectious aetiology of obesity would stimulate research to assess the contribution of infectious agents to obesity and possibly to prevent or treat obesity of infectious origin. A recently published review article sets out to do just that (Infectobesity: obesity of infectious origin. Adv Food Nutr Res. 2007 52: 61-102)
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The first obesity-promoting pathogen to be reported was canine distemper virus, a paramyxovirus which infects dogs (A virally induced obesity syndrome in mice. 1982 Science 216: 885). Although this was an interesting observation, since canine distemper virus does not infect humans, comparatively little was made of this finding. But how could a virus infection cause animals to become obese? In 1982 Michael Oldstone and colleagues reported a novel way by which viruses may cause disease, the “hit-and-run” model (Virus-induced alterations in homeostasis: alteration in differentiated functions of infected cells in vivo. 1982 Science 218: 1125-1127). The virus replicates in cells which make growth hormone, disrupting homeostasis and decreasing growth hormone synthesis but without producing any cell death or inflammation. The effect of CDV on the hypothalamus may initiate changes that would continue to promote obesity in animals even months after the acute infection, suggesting a “hit-and-run” effect may have occurred (Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus. J Virol. 1999 73:7317-7327).
In 1983, Rous-associated virus-7 (RAV-7) was the second pathogen reported to cause obesity. RAV-7 is an avian retrovirus http://www.microbiologybytes.com/virology/Retroviruses.html found in domesticated poultry (Rous-associated virus type 7 induces a syndrome in chickens characterized by stunting and obesity. Infect Immun. 1983 39: 410-422). In this case, a decrease in thyroid hormone levels is the major metabolic change that may explain the obesity observed.
Chlamydia pneumoniae is the first bacterium reported to be associated with increased body mass index (BMI) in humans. A number of epidemiological studies have linked infection with this organism to increased weight, although other studies have failed to find any connection. Unlike the organisms previously mentioned, experimental inoculation of animals with this organism to study the effect on body weight has not been reported, and so the link remains somewhat uncertain.
Scrapie is a neurodegenerative prion disease of sheep and goats. Much of the work with scrapie has been performed using mice as a model, and scrapie has been reported to cause obesity in mice. Unlike other biological properties of scrapie, this effect is not dependent on the strain involved, although it is dependent on the route of inoculation. Scrapie-induced obesity is related to changes in the central nervous system (CNS) and neuroendocrine dysfunction in infected mice. Although a number of human prion diseases are known, the relevance of these findings in rodents to obesity in humans has not been established.
Borna disease virus (BDV) is an enveloped, nonsegmented, negative-stranded RNA virus belonging to the Mononegavirales. Infection with BDV causes psychological as well as physical symptoms. BDV can cause obesity in experimentally infected rats, although only certain strains of the virus seem to do this. In this case, weight gain may be due to inflammatory lesions due to virus antigen expression in brain, especially in the hypothalamus, which is known to regulate body weight and food intake.
Finally, four strains of adenovirus have been reported to be adipogenic pathogens. Avian adenovirus SMAM-1 causes fat deposition (adiposity) in chickens, but also shows a serological association with human obesity (Association of adenovirus infection with human obesity. Obes Res. 1997 5: 464-9). This was the first virus to be linked with human obesity. It has been suggested that SMAM-1 infection could impair normal liver function, causing fatty liver and decreasing cholesterol and triglyceride levels in the blood. Subsequently, adenovirus types 5, 36 and 37 have also been shown cause obesity in animals. Of these, Ad-36 is the best studied. Sero-epidemiological studies show association between Ad-36 antibodies and human obesity, although the exact mechanism of
adipogenic action in vivo remains unknown. Of the 50 known serotypes of human adenovirus, only these three seem to cause obesity.
The jury is out on the significance of these findings to public health, but with increasing emphasis on obesity, they cannot safely be ignored. In the meantime, unless you’re listening to this podcast in the gym, get off your butt and take some exercise!
Acknowledgment: My thanks to Dr Nikhil Dhurandhar for his assistance with this article.
Dear author,
thank you for an interesting article. I’d like to know, though, what you think about the theory that exposure to BPA as a result of increasing plastic particles in our environment contributes to the obesity epidemic.
Here is the article where I found this information.
Thank you,
Julia K.
I’ll let others comment on Frederick vom Saal’s recent work on bis-phenol and obesity:
http://www.google.com/search?&q=+%22vom+Saal%22+obesity
[...] unknown. Of the 50 known serotypes of human adenovirus, only these three seem to cause obesity. Infectobesity: the bugs that make you fat « MicrobiologyBytes m (always peccable, sometimes [...]
I’m as fascinated by the new research into gut flora as the next girl, but my brain brakes lock at the assumption that obesity is actually an epidemic.
It could be a reinterpretation of the data, it could be a sign of the increased health of the population, it could be a confusion of cause and effect as regards disease, and it could be a conflation of the concepts of “overweight” and “obese” and “morbidly obese.”
Frankly, I think it is also largely a factor of aesthetic obesity. Being UNDERweight is associated conclusively with ill health but few people are evangelizing the issue of not eating enough.
I understand that special e-coli strains are being sold as probiotics, on the idea that bacteriodetes are better for attaining a thin stature. I contacted the pharmaceutical company in Germany and was told that the US will not permit them to be imported as we do not recognize any e-coli strains as being probiotics or even medicine.
Hello; author yes, I would have to agree with you here on the heart disease problems that link back to being overweight we are faced with in the world today. Day in and Day out we all are faced with the important meal decisions of creating a nice low fat supper for our family or the quick and easy Fast Food option and I would say that 78-80% of the US would chose the later because of the quick & easy solution to the problem at hand. If you want to learn more about the number 1 killer in the USA today Heart Disease please visit:
http://www.heart-condition-guide.com
Great reading