When looking at the obesity epidemic around the world, one thing becomes clear: it is complicated!
For years we have been told to eat less and exercise more. And while that is good, healthful advice, it doesn’t seem to be curing the obesity epidemic. According to the World Health Organization, obesity has doubled since 1980. Worldwide in 2014, 1.9 billion adults were overweight.[ref] About 70% of people in the US are now classified as overweight or obese.
Can obesity be triggered by a virus?
It seems odd to think about obesity being caused by an infectious disease. But there is an abundance of evidence showing that, for some people, this is likely true.
There have been several interesting studies linking obesity to a viral infection, specifically an adenovirus.
Adenovirus is a family of viruses with many different species causing a variety of symptoms in humans as well as other animal illnesses.
Examples of adenoviruses include respiratory illnesses (common cold) in humans and kennel cough in dogs (Canine adenovirus 2).
In humans, adenoviruses can also cause gastroenteritis, croup, bronchitis, pneumonia, and more.[ref ] Thus, adenoviruses are both varied and very common. And now certain species of the adenovirus have now been linked to adipogenesis (making of fat cells) in humans.
From a 2012 article titled “Is Obesity Caused by an Adenovirus?” by Nikhil Dhurandhar:
Among the known adipogenic pathogens, some induce obesity in animal models, whereas others are associated with human obesity. Adenoviruses are the only infective agents reported to be linked with adiposity in both experimental animal models and naturally infected humans, which make them promising candidates for investigating their role in human obesity. SMAM-1, an avian virus, is the first adenovirus reported to increase adiposity and the first virus reported to be associated with human obesity.[6,7] Adenovirus Ad-36 is the first human virus reported to cause obesity in animals.[8–11] Ad-36 is also associated with human obesity. Reports about the adipogenic role of additional human adenoviruses, Ad-5 and Ad-37, followed.[12,13] Thankfully, commonly prevalent human adenoviruses Ad-2 and Ad-31, and avian adenovirus chick embryo lethal orphan are not adipogenic.[9,12][ref]
That article goes on to review quite a few studies on the Adenovirus Ad-36 and its association with obesity. Twin studies in humans show that the Ad-36 positive twins to be “significantly heavier and fatter as compared with their antibody-negative counterparts”.
A 2005 study found that adenovirus-36 is associated with obesity, and it is also associated with lower serum cholesterol and triglycerides.[ref] Another study revealed that “Ad36, a human adenovirus, increases TNFα and MCP1 mRNA in adipose tissue, yet improves glycemic control in mice.”[ref]
A 2014 study found that a connection to both Adenovirus-5 and adenovirus-36 and obesity in children. From this study: “The presence of adenovirus-5-specific antibodies was 28.3% and 6.6% in the obese children and in non-obese children, respectively (P = 0.02). The frequency of adenovirus-36-specific antibodies was significantly greater (P = 0.018) in the obese children (26.6%) than in the non-obese children (10.0%). Serum leptin levels of the obese group were significantly higher than that of the non-obese group (P = 0.000).”[ref]
A 2015 Turkish study came up with similar results for adenovirus-36: “Adv36 positivity was determined to be 27·1% and 6% in obese and non-obese children and 17·5% and 4% in obese and non-obese adults, respectively. There was no difference with regard to total cholesterol, low-density lipoprotein, triglyceride, tumor-necrosis-factor-alpha, and interleukin-6 levels (P > 0·05). However, there was a significant difference between groups in terms of leptin levels (P < 0·05).”[ref]
In Feb. 2015 a study on Adenovirus-9 found “AdV9-infected subjects presented higher body weights, BMIs, WHR, and central obesity.”[ref]
A July 2012 study found that Adenovirus-37 was not associated with obesity, but it was associated with non-alcoholic fatty liver disease.[ref]
So how does this tie into genetics? We know that some people are genetically protected from certain viruses such as the Norovirus.(Gut Health and Your Genes) HIV, herpes, and other viruses are attenuated by genetic polymorphisms. Could there be a genetic tie to a person’s reaction to the adenovirus? Probably. But I don’t think the science is there yet to say for sure.
Below are several genes that are involved in adenovirus infection and obesity.
An October 2011 study looked at the impact of the adenovirus-36 infection on PPARγ. Interestingly, the study is looking at Ad36 as having an action similar to thiazolidinediones (TZD), a drug that lowers insulin resistance in diabetes but can also cause weight gain. The study found that Ad36 up-regulates PPARγ as well as improving glycemic control.[ref]
PPARγ, a nuclear hormone receptor, is present in fat tissue and is involved in the regulation of fatty acid storage and glucose metabolism. It is encoded by the PPARG gene which is a member of the peroxisome proliferator-activated receptor family. From Wikipedia: “The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice fail to generate adipose tissue when fed a high-fat diet.” Polyunsaturated fatty acids activate PPAR gamma. And while it may be responsible for fat storage, a study showed that “ligand-activated PPARγ decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells.”[ref]
PPARG gene polymorphisms have also been studied in reference to high-fat diets and, separately, cardiovascular disease. For the rs1801282 SNP, the G allele (23andMe orientation) was associated with much lower rates of heart disease.[ref] A meta-analysis looked at 60 studies of the rs1801282 SNP and found that those with the G allele had a reduced risk of Type 2 diabetes.[ref] A 23andMe blog post discusses the impact of diet on the variants of rs1801282. Those with the G allele seem to do well on a low-fat diet but have increased weight gain on a high-fat diet.[ref]
I haven’t found any studies directly looking at adenovirus-36 infections in relation to PPARG polymorphisms. But it seems that there might be an association between the amount of weight gained due to the ad-36 virus and a person’s PPARG polymorphisms.
A 2011 study looked at the method by which the adenovirus-36 increased adiposity. It found that in addition to PPAR-gamma, CEBP alpha was upregulated. According to the NIH, “Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis.”[ref]
A 2008 study found that those with the A/A genotype of rs12691 had higher triglycerides than those with the wildtype. The conclusion was: “Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.”[ref]
Heart Health and Virus Receptors:
Coxsackie and adenovirus receptor (CAR) is encoded by the CXADR gene. This receptor is a receptor for the Coxsackie B virus and adenovirus 2 and 5.[ref] CARs have been studied in conjunction with its involvement in virus-mediated myocarditis and, more recently, as a risk factor in ventricular fibrillation.[ref] A polymorphism near the CXADR gene, rs2824292, has been found to be associated with levels of expression of CXADR. “Individuals carrying one or two copies of the risk allele (A/G or G/G genotype) displayed significantly lower (0.6 fold) CXADR mRNA expression compared to individuals with the non-risk (A/A) genotype.”[ref] That study did not look at an association with the adenovirus infection in reference to the polymorphism.
Mulberry extract has shown to reduce Adenovirus 36 replication in mice. It brought about a reduction in weight and in pro-inflammatory cytokines.[ref] It would be great to see a study that looked at mulberry extract in humans in reference to Ad-36.
Vitamin D – In a study on children with obesity and Ad-36, the results showed that increasing vitamin D levels modified the effect of the adenovirus on adiposity.[ref]