[Subjectivist]

$this->bbcode_second_pass_quote('', 'V')irus-Induced Obesity in Humans

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Recognizing that a particular adenovirus can cause obesity changes perceptions about this condition and strategies for dealing with it

Richard L. Atkinson
AUTHOR PROFILE: Atkinson: a Focus on Virus-induced Obesity and No Plans To Retire

SUMMARY
➤ Infecting animals, including rodents and nonhuman primates, with human adenovirus 36 (Adv36) leads many of them to develop obesity.

➤ Adv36 infection is found in about 30% of obese human adults; among children, obesity correlates with Adv36 infection even more strongly than among adults.

➤ Adv36 infects humans and animals transiently, but viral DNA persists for extended periods, altering host metabolism and responses to stimuli or treatment.

➤ A single Adv36 gene appears responsible for disrupting host physiology and causing obesity.

➤ New government policies and scientific and treatment strategies are needed to address virus-induced obesity.


In 1998, offıcials of the World Health Organization (WHO) declared a global epidemic of obesity, recognizing the steady rise in its prevalence in both developed and developing countries since about 1980. Obesity, defıned as a body mass index (BMI in kg/m2) value of at least 30, doubled among US adults from 1980 to 2000, and tripled in children in the United States and other countries, including England, China, Thailand, and Korea. In women, the prevalence of obesity in Albania, Jordan, Panama, Paraguay, and South Africa is equal to or greater than that in the United States. Although some experts point to increased food intake, including of fast foods, and decreased activity, these factors do not explain the rise of obesity in developing countries.

Instead, this abrupt shift in the global prevalence of obesity appears to fıt the pattern of an infectious epidemic. Several events during the late 1970s appear to be consistent with this hypothesis. For example, soon after commercial chicken growers in Mumbai, India, noted increased deaths among their flocks, an Indian microbiologist identifıed an adenovirus, SMAM-1, that was infecting chickens and lowering immune functions, thus enabling other infectious agents to kill a higher percentage of chickens than usual. Moreover, when infected with SMAM-1, chickens developed increased body fat. Subsequent experiments in which chickens were deliberately infected with SMAM-1 reproduced the obesity seen when they were naturally infected. Meanwhile, some humans developed antibodies to this chicken virus.

Separately in 1978, scientists isolated adenovirus 36 (Adv36) from humans. Later, analysis revealed that this virus has fewer DNA sequences in common with the other approximately 50 human adenoviruses. Moreover, antibodies that recognize Adv36 do not cross-react with more than 40 other human adenoviruses that were tested. These fındings led scientists at the University of Wisconsin to speculate that Adv36 arose from SMAM-1 and that it not only infects humans but also can make them obese. Although not proved, other studies in humans and experiments in animals lend support to this hypothesis.

Adv36 Induces Obesity in Animals

Adv36, which infects humans, also infects other animal species, including chickens and mice, increasing body fat and lowering serum cholesterol and triglycerides (Table 1). Whenatkt1 infected, total body fat and fat inside the abdominal cavity (visceral fat) increases from 50 to 100% in chickens and mice over a period of weeks to months. The animals gain fat without changes in diet and activity. Mice infected with Adv36 easily pass the virus when in contact with uninfected mice.

Adv36 also infects monkeys, leading to increases in body weight through buildup of fat. In one study, investigators at the University of Wisconsin collected blood from 15 monkeys over 7 years, and then tested stored serum for antibodies against Adv36. Nearly half the monkeys had antibodies at the start, and the others developed them during the study through naturally occurring infection. Once antibodies appeared in blood, body weight began to rise in all the monkeys while serum cholesterol levels fell.

In another set of experiments, monkeys were inoculated intranasally with Adv36 and compared to uninfected animals over a 7-month period. The infected monkeys gained four times as much weight and increased body fat by 60% more than did uninfected animals. Serum cholesterol decreased signifıcantly in infected animals but did not change in the uninfected animals. Although live virus was recovered during the fırst 2 weeks after infection (and from feces 2 months after infection), at 7 months it could no longer be isolated from any of them. However, Adv36DNA was still found in brain, lung, liver, muscle, and adipose tissue. Thus, Adv36 DNA persists in tissues for long periods and might be responsible for chronic changes in biochemistry and physiology among infected animals.

Adv36 leads to obesity in 60-70% of infected chickens and mice, but in 100% of infected monkeys. Similarly, the paradoxical effect of Adv36 reducing serum lipid levels is seen broadly among infected rodents, chickens, and monkeys.

Adv36 also Induces Obesity in Humans

Adv36 viral infections in adult humans strongly correlated with obesity and lowered serum cholesterol and triglyceride levels, resembling changes seen in Adv36-infected animals. Among 500 adults in three U.S. cities, Adv36 infected 30% of obese adults but only 11% of nonobese adults. Infected individuals were on average 9 BMI units heavier than were the uninfected (P< 0.001), while serum cholesterol was 34 mg/dl lower in infected individuals, the same decrease seen in monkeys.

The percent of Adv36 infection among obese adults varies from 6% in the Netherlands and Belgium to 65% in Italy, but averages about 30% in most countries. The correlation between obesity and infection was not seen in adults in the Netherlands or among military personnel in San Diego, Calif. The overall prevalence of infection was 37% among military personnel, but higher among black and Hispanic people compared to whites. Unlike animals, serum lipids vary in humans among different studies.

It is diffıcult to explain some of these inconsistencies. One possibility is that when the Adv36 strain began infecting humans about 1980, the fırst populations that were infected and obese stood out from others. With time, however, more people were infected, earlier infected individuals stopped gaining weight, and antibody levels in some long-infected individuals fell. In Korea, for example, the prevalence of Adv36 antibodies in obese individuals is slightly higher but not statistically different from those in normal or overweight subjects.

atkt2However, the correlation between Adv36 infection and obesity is consistently high among children (Table 2). The prevalence of this infection ranges from 22 to 30% in obese children but from 7 to 14% in nonobese children. Among children in San Diego, for example, Adv36 infection prevalence was 22% among the obese compared to 7% among nonobese children, and infected obese children weighed 16 kg more than uninfected children. Meanwhile, the prevalence of Adv36 infection among obese children in Korea is 30%, but only 14% among nonobese children. The patterns of serum lipids in infected children in Korea differ from those among infected U.S. adults. These differences might arise from a variety of factors, including age, race, geography, diet, and duration of infection.

How Adv36 Infects Mammals and Acts Directly on Cells

Adv36 follows a typical adenovirus pattern of events, causing mainly upper respiratory but also sometimes gastrointestinal symptoms. Adv36 was fırst isolated from a stool specimen from a diabetic child in Germany who had acute diarrhea. Although the strain can be isolated from their feces, Adv36-infected animals, including monkeys, do not develop diarrhea. Individuals become infected with Adv36 after being exposed to droplets from other infected individuals who are coughing or sneezing, and infection may also occur via fecal-oral transmission. From cough droplets, the virus invades the upper respiratory epithelium, and its DNA enters cells and migrates to the nucleus to replicate without being incorporated into host DNA. Early viral genes disable host cell apoptosis, ensuring viral DNA replication.

atkt3The host epithelial cells die, releasing viral particles into the blood and they infect other tissues. Although Adv36 invades differentiated cells of multiple organs, it does not replicate or, if so, only slowly. However, in differentiated cells, viral DNA turns on transcription factors and enzymes that produce obesity (Table 3).

After infecting fat cells or preadipocytes in vitro, Adv36 increases the rate of differentiation and accumulation of lipid. Its major targets appear to be phosphatidylinositol 3-kinase (PI3K) and Ras pathways, triggering an increase of glucose receptors in the cell membrane, thereby enabling cells to take up increased levels of glucose. Adv36 also increases production of fatty acid synthase (FAS), a key enzyme in the pathway in which glucose is converted to fatty acids. Increasing cellular glucose and FAS leads to increased fat within fat cells. Adv36 also induces peroxisome proliferator-activated receptors (PPAR), leading to differentiation of adult stem cells within adipose tissue and resulting in higher numbers of fat cells.

Adv36 infects other cell types in vitro, leading to similar changes in muscle, liver, and breast cells as well as in primary adult human stem cells derived from adipose tissue. When monkeys are infected with Adv36, viralDNAis found in brain, lung, liver, muscle, and adipose tissue. After 7 months, viral DNA can be found but live virus can no longer be recovered from such sites in animals.

When Adv36 infects cells in vitro, there are changes in cytokines, including increased expression of IL-1α, IL-6, IL-11, interferon, and adiponectin, which in vivo can improve insulin sensitivity and lower serum glucose. The virus lowers leptin expression and secretion in fat cells, which may contribute to obesity in vivo.

The E4orf1 gene of Adv36 is crucial for mediating all its cellular and molecular effects. Blocking the E4orf1 gene also blocks fat-inducing effects. Further, inserting this gene into another virus makes it capable of stimulating fat formation. The Adv36 E4orf1 gene has less homology to those of other adenoviruses, apparently accounting for differences in metabolism in infected cells and individuals.

Adv36 Infections: Broader Implications

Adv36 infections occur naturally in large numbers of humans and other species, and the virus alters various molecular, biochemical, physiological, and clinical characteristics of cells and organisms that it infects. For investigators working with everything from specifıc cell types to humans, the possibility of unsuspected Adv36 infection is of concern because it may alter experimental variables. For clinicians, Adv36 infections may alter responses of patients to drugs or other treatments. For example, because Adv36 increases glucose uptake and improves insulin sensitivity, it might alter a diabetic patient's response to antidiabetic drugs and lead to hypoglycemia. Another study showed weight loss on a reduced-calorie diet was greater in individuals with Adv36 infection.

Having an infectious agent responsible for obesity forces all of us to reconsider this condition, which is widely held to be self-inflicted through inappropriate diet and activity levels. Health insurance providers typically limit their coverage for treating this condition, some employers will not hire the obese, while others insist that they enroll in weight reduction programs or pay higher rates for health insurance. These attitudes need to change with the knowledge that anyone susceptible to the Adv36 virus might develop obesity. Meanwhile, additional research is needed to better understand this virus and how to prevent and treat infections that might account for part of the worldwide obesity epidemic that began during the 1980s.

Richard L. Atkinson is Director, Obetech Obesity Research Center and Clinical Professor, Department of Pathology, Virginia Commonwealth University Richmond, Va. Financial Disclosure: The author is the owner of Obetech, LLC. This company provides assays for adenoviruses that produce obesity and has several patents in the area of virus-induced obesity.

[Strummer]

"Diet and exercise aren't effective," because the calories just appear out of thin air!

[Subjectivist]

$this->bbcode_second_pass_quote('', 'T')he top scientist guiding the U.S. government’s nutrition recommendations made an admission last month that would surprise most Americans. Low-fat diets, Alice Lichtenstein said, are “probably not a good idea.” It was a rare public acknowledgment conceding the failure of the basic principle behind 35 years of official American nutrition advice.

Yet the experts now designing the next set of dietary recommendations remain mired in the same anti-fat bias and soft science that brought us the low-fat diet in the first place. This is causing them to ignore a large body of rigorous scientific evidence that represents our best hope in fighting the epidemics of obesity, diabetes and heart disease.

The Dietary Guidelines for Americans—jointly published by the U.S. Department of Agriculture (USDA) and the Department of Health and Human Services (HHS) every five years—have had a profound influence on the foods Americans produce and consume. Since 1980, they have urged us to cut back on fat, especially the saturated kind found mainly in animal foods such as red meat, butter and cheese. Instead, Americans were told that 60% of their calories should come from carbohydrate-rich foods like pasta, bread, fruit and potatoes. And on the whole, we have dutifully complied.

By the turn of the millennium, however, clinical trials funded by the National Institutes of Health (NIH) were showing that a low-fat regime neither improved our health nor slimmed our waistlines. Consequently, in 2000 the Dietary Guidelines committee started to tiptoe away from the low-fat diet, and by 2010 its members had backed off any mention of limits on total fat.

Yet most Americans are still actively trying to avoid fat, according to a recent Gallup poll. They are not aware of the USDA’s crucial about-face because the agency hasn’t publicized the changes. Perhaps it did not want to be held responsible for the consequences of a quarter-century of misguided advice, especially since many experts now believe the increase in carbohydrates that authorities recommended has contributed to our obesity and diabetes epidemics.

[Keith_McClary]

$this->bbcode_second_pass_quote('Strummer', '&')quot;Diet and exercise aren't effective," because the calories just appear out of thin air!

[dissident]

$this->bbcode_second_pass_quote('Strummer', '&')quot;Diet and exercise aren't effective," because the calories just appear out of thin air!

[AgentR11]

I have mixed feelings on the whole diet/obesity thing. I do know this, when I was getting back into shape, I tracked everything, weighed everything I ate and used a VO2max proxy calibrated HR monitor to get realistic calorie burn numbers. During the 6 months I tracked meticulously, (calories burned - calories consumed) / 3500 equaled the ~30 pound of fat loss during the same period. It was really pretty shocking how accurate it was; I did weigh food as opposed to eyeball it, and didn't use the ridiculous numbers some exercise machines report though. [overall went from 250 to 180, and am trying to stabilize my weight at about 190. I'm stronger at 200, faster at 180.. so split the difference.. aiming to run a 6min mile at 50... can do 6:25'ish currently]

I'm moderately insulin resistant, without exercise, my bG will top out 1hr after eating just below 200; but with substantial exercise stimulus it stays below a reasonable 140 (interesting difference between hepatic insulin resistance and muscular, hepatic responds longer, but less strongly, but only to heavy resistance exercise; whereas muscular responds stronger, but for less than a day after sustained aerobic (1hr+ 75% hr max).

The caveat here, is that doing what I did (and do) is extremely painful. I am ravenously hungry often, and often enough when my gut is mechanically "full". That really sucks fwiw. My conclusion from all this, is that once you're down this rabbit hole of insulin resistance, messed up leptin response, etc; you're screwed. You *can* technically control your weight with diet and exercise, but it requires meticulous record keeping and a lot of continuous pain. That's just the way it is.

So the "diet and exercise" pimpsters really aren't lying, they're just selling something that they know almost no one can comply with; so they sell their book/program, make some money, a few folks chime in, "ooooo it worked" (because they were able to make the cal in - cal out thing happen for a while); but the pain eventually overwhelms the customers, they can't sustain the program, fall off, and fail; but they blame themselves because they didn't stay with the program. When in reality, only a masochistic psychopath could. (not too flattering towards myself.. but oh well)

Just my take on what I experienced.

And no, the low carb thing didn't solve the hunger deal, it just gave more days of being stuffed and starving at the same time. Pass.

Weigh it, count it, x-y rules the world.

[dohboi]

Agent, you are an inspiration. Really. Thanks for sharing that.

[Keith_McClary]

Obese Crash-Test Dummies Being Developed
$this->bbcode_second_pass_quote('', 'O')ct. 31, 2014 -- New crash-test dummies are being developed to reflect the fact that many Americans are obese.

Currently, a typical crash-test dummy represents a person who is about 167 pounds and not overweight. New dummies under development are based on the measurements of a 270-pound severely obese person, ABC News reported.

The updated dummies are being created by Humanetics, the only U.S. producer of crash-test dummies. Testing on the larger dummies will begin by the end of this year and they'll be available for wider use sometime next year, according to Humanetics CEO Chris O'Connor.

"Studies show that obese drivers are 78 percent more likely to die in a car crash," O'Connor told ABC News.

[dissident]

If there is a "cure" it is exercise. Not low fat diets. The problem is doing serious amounts of exercise, day in and day out. The insulin resistance defect reminds me of sickle cell anemia. The latter is a side effect of partial genetic adaptation to malaria while the former is characteristic of groups who had to survive under harsh food supply conditions. Type II diabetes is rampant amongst North American aboriginals.

True physical activity does wonders for Type II diabetes metabolisms. If we had to be physically active to feed ourselves then it would be a different state of health. But we spend our time in front of the screen, at work and and home.

[dohboi]

Agent was talking about low-carb, not low-fat, diets (but perhaps that's not what you were responding to).

Yes, exercise definitely has to be a factor. But recall that some use exercise to bulk up. So by itself, increased exercise it not a guarantee of weight loss.

[AgentR11]

I only brought up that particular diet form (lowcarb) because its a popular thing these days, and its sometimes suggested that it'll remove hunger while you lose weight. Maybe for someone it does, never did for me. My only concern with regard to ratios is any spike I might get in bG which is bad for all kinds of systems; so I avoid eating carb combinations that are fast; always cut them with some fat if I can, and the exercise keeps the insulin receptors working well enough.

A lot of people think its supposed to be a high protein diet, which is absolutely wrong. Past 1g/lb of body weight (which is a very high level), protein is pointless, its just a really expensive way to put glucose in your blood. (unless you're on HGH or other forms of better living through chemistry...) A low carb diet is high in fat, low in protein, and low in carbs. (think butter and cream, not piles of red meat and chicken breast).

"exercise to bulk up".... also a misnomer. Exercise is catabolic, it breaks down muscle. EATING and SLEEPING after the exercise stimulus causes your body to build muscle; though you'll need some chemistry on your side to make the magazine covers, or anything like that size. You know that big swimmer guy from the past olympics.. Mark something? He was *not* kidding about the scale of calories required to build muscle.

The final point I'd like to make, is weight loss is only important in the context of what your joints can handle. eg, past 200lbs, running with a full stride gets really painful, really fast; at 180 its smooth as can be. For health metrics, its fat loss you have to focus on; and there is a way to measure it. You sit in a closed bucket while someone with an air compressor squishes you and measures the difference. (aka "bodpod") Pretty easy, and provides as close to ground truth as you can get short of being dissected or imaged with a REALLY expensive machine.

[dohboi]

Thanks for the correction.

I was on a short-term lo-carb diet, and after about a week it made me really irritable. (Not that there are not always plenty of things worth being irritated about, of course, but I usually can avoid snapping at people who are being complete frigin idiots.)

[dohboi]

"you have to maintain a regular regime of aerobic exercise"

That may have been it. I had been biking pretty regularly, but we had a colds snap and work also got busy, so I didn't take the time to put in the exercise for a few days.

Thanks all for your perspectives.

[Subjectivist]

$this->bbcode_second_pass_quote('dohboi', '&')quot;you have to maintain a regular regime of aerobic exercise"

That may have been it. I had been biking pretty regularly, but we had a colds snap and work also got busy, so I didn't take the time to put in the exercise for a few days.

Thanks all for your perspectives.

[Subjectivist]

A person who has been living on the high carb standard American Diet (SAD) is very carb adapted. Their brain burns up too 120 grams of glucose a day. A person who has been low carb for several weeks transitions over to be a ketone burner for brain activity. The human brain can burn 120 grams of carbs, or 40 grams of carbs and 80 grams of ketones. Switching back and forth gives many people 'low carb flu' because their liver has to ramp up ketone production to make up for the lack of glucose in the diet. Coconut oil is all C12 or shorter fatty acids which the human body is predisposed to burn rather than store. If you eat it the short and medium chain fatty acids get taken out of the blood by the liver and converted into ketone bodies for the brain even if you are on a high carb diet. People with epilepsy and Alzheimer's disease often have a brain chemistry problem with getting energy from glucose so by flooding the brain with ketones you can improve their brain chemistry. Depending on the individual the improvement can be moderate to complete.

Low carb diets are being studied for cancer treatment as well because cancer cells can not use ketones, they only use glucose.


Dr. Peter Attia has a lot of information about all of this on his blog site.
http://eatingacademy.com

[kuidaskassikaeb]

This is kind of another theory of all the modern plagues. I read this book missing microbes. Its more about asthma, and colon problems, but obesity is in there, since it seems early use of antibiotics and C-sections are also associated with obesity. I liked the the book a lot. He even as an antibiotic doomsday scenario.

http://www.npr.org/books/titles/302897992/missing-microbes-how-the-overuse-of-antibiotics-is-fueling-our-modern-plagues