A Deeper Look into Adenovirus-36 and Obesity

This is the fifth of 6 guest posts on infection and chronic disease.

By Whitney Baker

My previous blog post examined the idea of an infectious etiology for obesity by a group of possible infectious agents. While these pathogens have been associated with obesity in humans or animals, their causative role in human obesity has not yet been established. So for this round, I thought I'd focus in on the bug showing the most evidence for human obesity: Adenovirus-36.

(More after the jump...)

First, a little background on Adenovirus [1]... it most commonly elicits respiratory illness; however, certain serotypes may also cause various other illnesses, such as gastroenteritis, conjunctivitis (pinkeye), cystitis (bladder infection), and rashes. Adenoviruses are double-stranded DNA viruses, with 51 immunologically distinct types able to cause human infections. The viruses tolerate adverse pH conditions and are unusually chemically and physically stable, allowing for prolonged survival outside of the body. All types are transmitted by direct contact, fecal-oral transmission, and occasionally through waterborne transmission (think unchlorinated swimming pools). Some have been shown to be endemic in certain parts of the world and often infection is acquired in childhood.

Specifically, Adenovirus 36 (Ad-36) typically causes respiratory and eye infections. But somewhere along the way, scientists noticed something special about Ad-36. In 2000, Dhurandhar et al found that "animals inoculated with Ad-36 developed a syndrome of increased adipose tissue and paradoxically low levels of serum cholesterol and triglycerides." Of note, this study did use comparison groups inoculated with other pathogens both in mice and chicken. [2] In a total of 3 experiments, Dhurandhar et al showed the prevalence of obesity in chickens and mice infected with Ad-36 versus control animals were 60-70% (infected versus control), and 100% of non-human primates that were infected with Ad-36 gained adiposity (infected versus control). [2-4] They also noted significant decreases in serum cholesterol and triglycerides.

Two human studies relating to Ad-36 have been performed. In a 2005 analysis of 502 subjects, significant (p

The mechanism in which Ad-36 induces obesity is understood to be due to the viral gene, E4orf1, which infects the nucleus of host cells. E4orf1 turns on lipogenic (fat producing) enzymes and differentiation factors that cause increased triglyceride storage and differentiation of new adipocytes (fat cells) from pre-existing stem cells in fat tissue. [6]

So, as Ad-36 has been found in 30% of obese people in the United States (and in only 11% of those nonobese), one has to wonder about the possibly of "Infectobesity": obesity of infectious origin. [7] The obesity epidemic does seem to mimic that of an infectious cause, but I think it is highly unlikely that all of America's (and the world's, for that matter,) growing waistlines are attributable to Ad-36. It indeed may play a role in pathogenesis, but obesity has a heterogeneous causality, really. There most likely is an infectious component to obesity, but more research needs to be done. For now, I'll stick to the notion of calories in

Whitney has been interested in infectious diseases since the 8th grade. She has a Bachelor's in microbiology and a Master's in Public Health in epidemiology. Two years after landing a university job in infectious disease epidemiology research, she began working toward a PhD in epi. Whitney's focus area is emerging zoonotic diseases- in particular, the epi of cross-species pathogen transmission from animals to humans- but she has no idea what she'll do when she's no longer in school.

Works cited

1. Adenoviruses.

2. Dhurandhar NV et al. 2000. Increased adiposity in animals due to a human virus. Int J Obes Relat Metab Disord 24:989-96. Link.

3. Kolesar JM et al. 2000. Direct quantification of AD-36 adenovirus DNA by capillary
electrophoresis with laser-induced fluorescence. Journal of chromatography. 744:1-8. Link.

4. Dhurandhar NV et al. 2001. Transmissibility of adenovirus-induced adiposity in a chicken model. Int J Obes Relat Metab Disord. 25:990-6. Link

5. Atkinson RL et al. 2005. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes (Lond). 29(3):281-6. Link.

6. Atkinson RL. 2008. Could viruses contribute to the worldwide epidemic of obesity? Int J Pediatr Obes. 3 Suppl 1:37-43. Link.

7. Pasarica M, Dhurandhar NV. 2007. Infectobesity: obesity of infectious origin. Advances in food and nutrition research. 52:61-102. Link.

Image from http://upload.wikimedia.org/wikipedia/en/0/0d/Adenovirus_4.jpg

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An "infectious etiology for obesity"?

Are you joking? Hmmm. Blaming a virus instead of, I dunno, eating six cheeseburgers and fries and pizza and chocolate cake and cartons of coke and Dorritos and.........

As comedienne Roseanne Barr used to say, if you're fat, just be fat and shut up!

By Mountain Man (not verified) on 16 Apr 2008 #permalink

Mountain man, I believe this is one of those few cases where we are actually on the same page. There's not too many foods out there that if you eat too much for too long, you won't get fat. Raw cabbage comes to mind.

The reasons for the he levels of obesity in this country are:

Sedentary Lifestyles (no excercise)
Fast Food
Processed Carbohydrates (all that refined sugar!)

We evolved to be hunter gatherers. 100,000 years ago we ate meat and berries. We weren't hunting down loaves of bread and setting traps for Krispy Kremes.

By boomer0127 (not verified) on 16 Apr 2008 #permalink

Oh, and don't get me started on the metabolism-destroying rubbish that is called the PUBLIC SCHOOL LUNCH. The food pyramid is soooo wrong on so many levels. Basing food intake for our children on this crap has done more damage to this country's future than any terrorist ever could.

By boomer0127 (not verified) on 16 Apr 2008 #permalink

last one - maybe the Ad36 prevalence is due to poor hygiene in public school cafeteria workers?

By boomer0127 (not verified) on 16 Apr 2008 #permalink

Change the direction of the greater than/less than symbol. Calories in means consumed and calories oout means expended. Obesity develops when calories in > calories out.

Could calories in > cclories out be an effect of Ad-36 because of changes in appetite-controlling hormones? Adipocyte hyperplasia may cause changes in leptin or adiponectin or other adipocyte hormones that lead to increased consumption. Have these hormones been checked [I/ve only looked at the abstracts].

One observation that would limit the level of "infectobesity" in the general population would be the low cholesterol & triglycerides, since they are generally higher as % body fat increases, especially in the case of Metabolic Syndrome.

By natural cynic (not verified) on 16 Apr 2008 #permalink

"Your fatness is quite treatable
I'm giving you this pill"
He gave me a prescription
Then handed me the bill
The man boobs they were quickly shed
Alas my sex life failed
I suffered from tenesmus
And pains that made me pale
"So sorry" said the doctor
"Its side effects I think
Here try these medications
They'll fix you in a blink"
My erections were spectacular
The wife was very pleased
But they gave me throbbing headaches
And made it hard to breathe
"So sorry" said the doctor
"It's side effects again
This brand new drug is excellent
It's called Voxabifen"
The headache stopped immediately
But chest pain took its place
My ankles swelled like footballs
And I lost my sense of taste
"That's easily fixed" the doctor said
And handed me more pills
"They'll lower your cholesterol
But sadly not your bills"
I took the pills for many months
The chest pain did abate
But the nausea was terrible
And alas I gained more weight

More pills were added to my list
They seemed to do the job
And then I got a nasty rash
Which spread down to my knob
My guts went into spasms
My bum leaked orange ooze
God help me if I farted
My wife was not enthused
The new svelte me was gone for good
The willy drooped again
A lump grew in my testicle
My chest filled up with phlegm
The prostate shrivelled to a pea
Libido gone for good
My wife got very tearful
I'd hug her if I could
The wife left me on Friday
She'd found another chap
She said I looked like bloody hell
And life with me was crap
I had a stroke on Sunday
I wasn't pleased with that
But the thing that pissed me off the most
Was that I was still FAT!

By quackquack (not verified) on 16 Apr 2008 #permalink

ooh did you try gastric bypass?

I like ur other one better,

Copyright the great yellow-bellied Crowe or what not

Ode to Robert Gallo (Cathy van Miert, 2008)

Bounder
Like a fanciful assumption
Like bad logic that's a wheel
Never ending, no abating
On increasing spinning spiel
Like a snowball down a mountain
Roll the egos of buffoons
Like a carousel of madness
Standing howling at the moon
Like a clock whose hands stopped turning
Once they saw Bob's ugly face
And the theory like an onion
Layered endlessly in space
Like the fantasies they find
In the windmills of Bob's mind

Logic twisted like a vortex
Down the rabbit holes of loam
These bad theories are so hollow
Where the truth light never shone
Like a parrot that keeps memeing
In its bird-brain little head
"HIV is deadly mortal
And you'll very soon be dead"
Like a clock whose hands stopped turning
Once they saw Bob's ugly face
And the theory like an onion
Layered endlessly in space
Like the fantasies you find
In the windmills of Bob's mind

Cash that jangles in Bob's pocket
Deaths of such insanity
Why the theory caught so quickly
When it was mendacity
Liars walk among the famous
And leave marks in history
Is the sound of four dark horsemen
Making Bob so jittery?
Bodies littering his conscience
But his conscience did a bunk
Unremembered nameless faces
And he doesn't give a funk
One day when this is over
And the world becomes aware
Human history won't forgive him
As he dangles in the air (from the Gallo's)

Like a fanciful assumption
Like bad logic that's a wheel
Never ending, no abating
On increasing spinning spiel
As the truth must soon unwind
Like the fantasies they find
In the windmills of Bob's mind

Copyright: Alberta Reappraising AIDS Society - January 12, 2008

Ms. Baker,

Great choice for a post, and well-researched! The twin studies and the E4orf1 mechanistic hypothesis are promising. As for antivirals, traditional methods of weight control are probably better...unless evidence emerges that infected obese people truly need pharmacological help in their struggle.

Natural cynic,

I see your point, but I read Baker's "calories in less than calories out" differently: it's a "notion" as she writes, that the best way to control weight is by balancing calories in and out. Because this is difficult, some people with weight problems might deny the notion in favor of a viral hypothesis.

Adele,

I continue to be underwhelmed with CVM's abilities as a "medical writer/researcher", but I trust we can all agree her poetry is downright brilliant.

Poet laureate qualities or no, it's a bit excessive to say the least to call for the violent death of a respected scientist, is it not? (Could you please post a link to that Gallo piece?) Not that Cathy seems to care much about the life and health of others: she claims to be currently filing and expanding a lawsuit with one apparent goal of denying HIV testing and treatment to African immigrants in New Zealand (kamerayangu dot blogspot dot com/2008/03/to-all-african-people-living-in-new.html).

And still there are those who feel denialism should simply be ignored.

By ElkMountainMan (not verified) on 17 Apr 2008 #permalink

Hi Elkman sorry I cant find it now my search isn't working, you can google it I copied it a couple months ago on Great Western YEllow bellied Crowes' site. Rats I have not copied the adress!!

Dont worry she is not threatening, any body. I always see her at mercola and places about B12 and stuff she is harmeless, funny!! She is PPAR Gamma Girl and hivbollyx or Cathy V.M. That is how I new bc I saw her poem before there.

Adele!!! What are you doing spoiling it all?!

Yhe answer is "yes damn it!! Cathy is very, very dangerous. I think some amendments to the terror and torture laws are in order here. Let's call in the two Johns, Yoo and Moore, for a presidential advisory panel on the legality of preemptively challenging human genitals with ulcer-causing microbicides.

Sir Predictable-To-The-Boring-Extreme OutragedMan, your qualities as a medical writer may well rival Cathy's (remains to be seen), but I sugest you leave the appreciation of poetry to the pros. First of all Cathy's poetry, while tolerable, is far from laureate level. Secondly, she is not calling for anyone's violent death - least of all a respected scientist. She is predicting that history in hindsight will send Gallo('s reputation) to the gallows.

In the future, if you want to preserve something for your Judgment Day FBI cyber files, try simply googling key words like the name of the rhyme, the author and the publisher.

On second thought, Adele is right: Cathy, while vicious in an almost pathological way, is likely thoroughly harmless. She has every intention of attacking Gardasil and making it difficult for African immigrants in New Zealand to get proper testing and treatment for HIV and AIDS, but she has demonstrated over the last month and more that she's not a serious threat to anyone's health but her own.

In this one forum, a popular science blog read around the world, she had a chance to defend her case before a mixed audience of friends and skeptics: that Merck lied about Gardasil and that HIV does or doesn't do whatever it is she suggests. In this one forum, Cathy's "Scoop" article was treated to a critical review. Yet in this same forum, Cathy has been unable to respond to her critics. Not that she has no interest: she visits this blog regularly (probably daily, as you and I do) and leaves insulting posts, always under a different screen-name. Accusing her opponents of ad hominem attacks, her responses are entirely ad hominem. Intending to convict Merck of lies about Gardasil, she lies about Merck. Hoping to prove I know nothing about electron microscopy, she shows her own ignorance of optical versus electron microscopy.

Even cooler puts Cathy to shame in debate, yes, cooler, who is at least familiar with (if he often misunderstands) the tiny sliver of science he has investigated. Cathy can correctly spell the names of medications she has taken, but little more. That's why, at least for now, she is indeed harmless.

Of course, the big lawsuit is always a week or two down the road for denialists. Maggiore is always a month away from bringing down the entire "paradigm", Parenzee is always about to win his appeal (proving what?) and Cathy is just as close to exposing the New Zealand government's racist conspiracy of "enforced HIV illness" (or effective, proven, and safe treatment for a potentially fatal infection). For now, though, I'll place the call to D.C. and call off the hordes of FBI investigators and CIA operatives you seem to think I have at my disposal. Then I'll go outside, split some wood and make sure the goat has water.

By ElkMountainMan (not verified) on 17 Apr 2008 #permalink

Sir Elkie,

Don't forget to oil your gun and, if you're milking that goat, give it a few minutes on 6000 degrees celsius before imbibing.

For now, I'll stick to the notion of calories in < calories out. For those who don't want to admit to calories in < calories out, then they can sit on the couch, secretly eat their ice cream, and wait for their Ad-36 vaccine.

It's an awful lot more complex than that, given the differences in metabolism that have been known about since the 1950s.

In 2000, Dhurandhar et al found that "animals inoculated with Ad-36 developed a syndrome of increased adipose tissue and paradoxically low levels of serum cholesterol and triglycerides."

This bit is quite fascinating. If infection by Ad-36 results in a favorable lipid profile despite increased adiposity, wouldn't that be a good thing? Provided of course that the reduction in cholesterol and triglycerides isn't just a transitional short term effect. If not, how is this paradoxical combination of high BMI accompanied by low serum lipid levels likely to affect lifetime risk of diabetes/atherosclerosis/heart disease/stroke/whatever?

By Stagyar zil Doggo (not verified) on 18 Apr 2008 #permalink

Carlie
How does that story prove your point? Lower metabolism just means its harder to get the calories out. I don't think that gives people an excuse to be fat. There are lots of things in life you need to work hard for. Being fit and healthy should be one of them.

How does that story prove your point? Lower metabolism just means its harder to get the calories out. I don't think that gives people an excuse to be fat. There are lots of things in life you need to work hard for. Being fit and healthy should be one of them.

I think the problem is that many of the commenters are conflating the scientific question of whether a virus can modify the metabolism of the host (why not?) and the another question about a possible consequence of this that some people will blame their obesity on a virus when it is probably only a minor factor.

By Chris Noble (not verified) on 18 Apr 2008 #permalink

Give Chris Noble some sort of commenters award for the reinjecting of clarity into an argument.

Excuse the trolls once again Tara, but I see Elkie still talking in circles and never telling us how Guardisil is supposed to work, nor is he responding to the critique of Howard Urnovitz that I posted way back here on fraudulent HPV cancer connection.

As always when the tactic of constructive dismissal is deployed by the gang, there's no recognition given to the other posts that support Cathy's arguments.

Without a clear demonstration of how HPV causes cervical cancer, Merck is perpetuating a fraud on the American people. They use a surrogate marker for cancer in the published reports, not the disease itself.

There are so many better ways that have been proven to prevent different types of cancer that shills like Elkie continually ignore. Oh that's right I almost forgot nothing can be proven in principle, antioxidants are nothing more than quackery, Resveretrol is simply snake oil and there's going to be an AIDS vaccine in a few ears.

Of course a little brainwashing by Big Pharma goes a long way when it comes to inconvenient truths. With technicians posing as scientists who've never learned how to think critically, it's actually child's play.

Repeat after me - nutraceuticals : there's no evidence ... there's no evidence ... there's no ....

BTW, Elkie, there IS technology that takes photographs (uses photons) down to the 10 nm level.

So big deal to your point, the question still stands whether one uses EM or PM: why can't we see HIV ex vivo and separate from other cellular material?

Look its Gene again!! He says,
TB and KSHV was not real until 1979 and doctors caused it over prescribing antibiotics!!

Sheesh Gene EM PM SHMEE M make up some new stuff I am yawning.

Gene, since you may not have had an opportunity to read the Vaccinations cause Immunology thread, here is what I wrote on electron vs. optical microscopy:

As MEC correctly notes, electron micrographs are not photographs. Light-based techniques (which allow "photography") are subject to a "limit of diffraction". This means that with standard light microscopy, one cannot differentiate particles smaller than a certain size: about 200 to 400 nanometers depending on your setup. Although numerous recent techniques have been applied to lowering this limit, including fluorescence applications, optical reconstruction, and materials-based approaches like ultra-thin lenses, the end product of at least some of these techniques is also not strictly speaking a "photograph".

There's been some fascinating work of late applying these new techniques to imaging HIV complexes inside the cell, yielding new insights into where the virus uncoats, how it gets to the nucleus, the reverse transcription assembly, etc.: studies for which EM is not well-suited.

Urnovitz? His "science" at least in this area is even less deserving of a response than Cathy van Miert's article. Certain HPVs are infectious and pathogenic, and immune techniques and PCR are very good at detecting them. If you won't believe until you've seen isolated virus from every patient with your naked eyes, then by all means continue to consider HPV a "molecular signature" of teen angst.

By ElkMountainMan (not verified) on 22 Apr 2008 #permalink