The Mysterious Virus That Could Cause Obesity

Randy is 62 years old and stands tall at six foot one. He grew up on a farm in Glasford, Illinois, in the 1950 s. Randy was raised with the strong discipline of a farming family. From the time he was five, he would get out of bed at dawning, and before breakfast hed put on his boots and jeans to milk cows, lift fodder, and clean the chicken coops. Day in and out , no matter the weather or how he felt, Randy did his physically demanding chores. Merely when his run was complete would he come into the kitchen for breakfast.

Tending to the chickens was hard workit involved getting into the pen, clearing birds out of their dirty cages, and shooing them into a holding enclosing. This process was always a little scary because the animals could be quite aggressive after being cooped up all night. On one of these occasions, when Randy was 11, a particularly large and perturbed rooster swung its claw and devoted him a good spurring on his leg. Randy felt the piercing of his scalp and squealed in pain. He said it felt like being gored by a thick fishhook. The rooster left a long gash, and blood streamed down Randys leg to his ankle. He operated back to the house to clean the wound, as chickens are filthy after a night in their cages.

Excerpted from The Secret Life of Fat: The Science Behind the Body’s Least Understood Organ and What It Entails for You by Sylvia Tara.W. W. Norton& Company

Some days later, Randy noticed a change in his appetite. He was constantly hungry. He felt drawn to food and thought about it all the time. He started feeing in between dinners and overeating where reference is ultimately sat down to dinner. Randy had always been a skinny child, but in the course of the next year, he gained about 10 pounds. His mothers thought it might be puberty, though it seemed a little early. His pudginess was also unusual given that everyone else in the family was thin. Randy was no stranger to discipline. He forced himself to feed less, switched to lower-calorie foods and exercised more. But by the time he was a teenager, he was bouncing between 30 and 40 pounds overweight. He says, I gained all of this weight even though these were some of my most active years on the farm.

Randys family supported his efforts to control his weight. They made lower-calorie foods, dedicated him time to exert, and didnt pressure him to eat things he didnt want. However, the committee continues to struggle with his weight through college. Randy kept thinking back to the moment everything changed. He had been the skinniest child among his friends. And then he got cut by that chicken.

The Curious Case of Indian Chickens

In Mumbai, India, Nikhil Dhurandhar followed his father Vinods footsteps in treating obesity. But Nikhil ran into the same obstacle that had bedeviled obesity doctors everywhere. The problem was that I was not able to produce something for patients that could have meaningful weight loss that was sustainable for a long time, he says. Patients kept coming back.

Fate intervened in Dhurandhars life one day was when he was meeting his father and a family friend, S. M. Ajinkya, a veterinary pathologist, for tea. Ajinkya described an epidemic then flaming through the Indian poultry industry killing thousands of chickens. He had identified the virus and named it using, in part, his own initialsSMAM-1. Upon necropsy, Ajinkya explained, the chickens were found to have shrunken thymuses, enlarged kidneys and livers, and fat deposited in the abdomen. Dhurandhar believed this was unusual because typically viruses cause weight loss , not gain. Ajinkya was about to go on, but Dhurandhar stopped him: You just said something that doesnt sound right to me. You said that the chickens had a lot of fat in their abdomen. Is it possible that the virus was making them fat?

Ajinkya answered honestly, I dont know, and exhorted Dhurandhar to study the question. That fateful dialogue defined Dhurandhar on a path to analyse as part of his PhD project whether a virus could cause fat.

Dhurandhar pushed ahead and arranged an experiment using 20 healthy chickens. He infected half of them with SMAM-1 and left the other half uninfected. During the experiment, both groups of chickens devoured the same quantity of food. By the end of the experiment, only the chickens infected with the SMAM-1 virus had become fat. However, even though the infected chickens were fatter, they had lower cholesterol and triglyceride levels in their blood than the uninfected birds. It was quite paradoxical, Dhurandhar recollects, because if you have a fatter chicken, you would expect them to have greater cholesterol and circulating triglycerides, but instead those levels went in the wrong direction.

To confirm research results, he set up a recur experimentation, this time using 100 chickens. Again, only the chickens with the SMAM-1 virus in their blood became fat. Dhurandhar was intrigued. A virus, it seemed, was causing obesity. Dhurandhar thought of a route to test this. He arranged three groups of chickens in separate enclosures: one group that was not infected, a second group that was infected with the virus, and a third group that caged infected and uninfected chickens together. Within three weeks, the uninfected chickens that shared a cage with infected ones had caught the virus and gained substantial amounts of body fat compared to the isolated uninfected birds.

Fat, it seemed, was in a position to be contagious.

Now, Dhurandhar is a man of science. He is rational and calm. But even he had to admit that the idea was startling. Does this mean that sneezing on somebody can transmit obesity? This now seemed possible in animals, but what about humans? Injecting the virus into people would be unethical, but Dhurandhar did have a style to test patients to see if they had contracted the virus in the past.

Dhurandhar says, At that time I had my obesity clinic, and I was doing blood tests for patients for their treatment. I believed I might just as well take a little bit of blood and exam for antibodies to SMAM-1. Antibodies would indicate whether the patient was infected in the past with SMAM-1. The conventional wisdom is that an adenovirus for chickens does not infect humen, but I decided to check anyway. It turned out that 20 percent of the people we tested were positive for antibodies for SMAM-1. And those 20 percentage were heavier, had greater body mass index and lower cholesterol and lower triglycerides compared to the antibody-negative individuals, just as the chickens had. Dhurandhar observed that people who had been infected with SMAM-1 were on average 33 pounds heavier than those who werent infected.

The Pounds Keep Coming

While Nikhil Dhurandhar was in India seeking his curiosity about fat, Randy was looking for solutions of his own. After a brief stint as a educator he moved back to the family land in 1977 because he loved farming.

Randy married and had four children. At household dinners and holiday assembles, he feed alongside everybody else, but tried eating less than the others. Still, his weight ballooned; by his late 30 s he had topped 300 pounds. He remembers feeling hungry all the time, though even when he abstained it didnt assistance him lose weight. I could have several good weeks of feeing stringently, much less than others around me, but if I went off my diet for simply one mealboom, the weight would come back.

The effort to control his eating, even when it was successful, stimulated Randy miserable: I cant tell you what it is like to be hungry all the time. It is an ongoing stress. Try it. Most people who give advice dont have to feel it.

In the fall of 1989, Randy applied for a commercial drivers license. The application involved a medical exam. After his urine exam, the nurse asked Randy if he felt all right. Normal for the day, he responded. But the nurse told Randy he would have to give a blood sample because she thought the lab had spilled glucose solution into his urine sample. The blood work showed that Randys glucose level was near 500 mg/ dL( a normal reading is 100 ). The laboratory hadnt made a mistake with the urine sample after all; Randys numbers were just off the following chart. Alarmed, the nurse notified Randys doctor, who then tested him for fasting blood sugar levels. The results showed that Randy had insulin resistance and severe diabetes.

At 40 years old and 350 pounds, Randy was in trouble. If he didnt fix this problem soon, he would start to develop serious complications of diabetes, including cardiovascular disease and nerve damage.

Having tried and failed multiple diets, Randy and medical doctors chose the best hope was a hospital program for severe diabetics. The faculty tested Randys blood often to decide the optimal dosage and timing of insulin injections to regulate his blood sugar. Randy learned about the Diabetic Exchange diet, which allots patients a specific number of servings of meat, carbohydrates, veggies, and fat. He cut out all refined carbohydrates, including bread. He says, I havent had a slice of bread or piece of pizza in years.

But would even this program be enough? Randy had always had a difficult time controlling his weight, though not for lack of trying. He had been fighting fat since his childhood by controlling sections, exercising, and avoiding social eating. But his discipline was no match for his own fat. Randy had to get his weight under control permanently. The hospital environment was helpful. However, despite strictly adhering to the diet, he only fell a few pounds.

The Virus in Americans

After taking on a postdoctoral fellowship at the University of Wisconsin, Madison under Dr. Richard Atkinson, Dhurandhar was excited to finally be at liberty to seek what he loved. He had an intense curiosity about viruses and was eager to get started determining answers. However, when he tried to get samples of the SMAM-1 virus that he had worked with in India, the U.S. Department of Agriculture refused to grant him an import license. He was deeply disappointed.

Unable to get SMAM-1, Dhurandhar approached a company that sells viruses for research. Their catalog listed some fifty human adenoviruses. He says, I was going to order the human adenovirus, but there was no the adenovirusthere were 50 different human adenoviruses! So I was stuck again. I wondered how do I go about this? Should we start number 1, number two, number three, number 50, 49, 48? So[ with] a little bit of guesswork and largely luck, we decided to work with number 36. We liked number 36 because it was antigenically uniquemeaning it did not cross respond with other viruses in the group, and antibodies to other viruses would not neutralize it.

That was a serendipitous selection. It turned out that Ad-3 6 had similar qualities to SMAM-1 in chickens. Atkinson believed Ad-3 6 might very well be a mutated sort of SMAM-1. When Dhurandhar infected chickens with Ad-3 6, their fat increased and their cholesterol and triglycerides lessened, just as had happened with SMAM-1. Dhurandhar wanted to make sure he was not getting a false positive, so he injected another group of chickens with a virus called CELO to ensure that other viruses were not also making fat in chickens. Additionally, he preserved a group of chickens who had not been injected with anything. When he compared the three groups, only the Ad-3 6 group became fatter. Dhurandhar then tried the experimentations in mice and marmosets. In every case, Ad-3 6 made animals fatter. Marmosets gained about three times as much weight as the uninfected animals, their body fat increasing by virtually 60 percent!

Now came the big question: would Ad-3 6 have any consequence on humans? Dhurandhar and Atkinson tested over 500 human subjects to see if they had antibodies to the Ad-3 6 virus, indicating they had been infected with it at some phase in “peoples lives”. His team found that 30 percent of subjects who were obese tested positive for Ad-3 6, but merely 11 percent of nonobese individuals dida 3 to 1 ratio. In addition , nonobese individuals who tested positive for Ad-3 6 were significantly heavier than those who had never been exposed to the virus. Once again, the virus was correlated with fat.

Next, Dhurandhar devised an even more stringent experimentation. He tested pairs of twins for presence of Ad-3 6. He explains, It turned out precisely the route we hypothesizedthe Ad-3 6 positive co-twins were significantly fatter compared to their Ad-3 6 negative counterparts.

Of course, its unethical to infect human subjects with viruses for research, so such studies cant be absolutely confirmed. But, Dhurandhar says, This is the closest you can come to showing the role of the virus in humen, short of infecting them.

A New Way to Manage FatStop the Blame

Randys physician had been treating him for years and knew that his patients fight was difficult and ongoing. The physician referred Randy to an endocrinologistRichard Atkinson at the University of Wisconsinwho was having some success with difficult obesity cases.

Randy went to see Atkinson, knowing that if he didnt get his fat under control, it was going to kill him. The first thing Randy noticed about Atkinson was that he was kind. He didnt induce Randy feel guilty about his weight. Other places put the blamed on you, Randy says. They go back into your past, what did you do to get here. It is very judgmental. Atkinson did none of that. He said okay we are here now, how do we fix it? He was very future oriented.

Atkinson had designed a long-term program to treat obesity. He explained to his patients that obesity is a chronic disease and they would be in treatment forever. In the first three months of the program, patients would meet several days per week and attend a lecture explaining obesity and the underpinnings of fat. After that, visits decreased to one every one to two weeks, then one every one to two months. Those who started regaining weight were asked to resume more frequent visits. Topics had to commit to the full program in order to enroll.

Atkinson also introduced Randy to his new postdoctoral assistant, a young scientist from India, Dr. Nikhil Dhurandhar. Dhurandhar analyzed Randy and analyzed his blood samples. Randy tested positive for antibodies to Ad-3 6, meaning he had likely been infected with the virus at some point in the past. Randy recollected being scratched by that rooster as a child, and that afterwards his appetite explosion and he started gaining weight rapidly. His troubles with food and rapid fat accumulationhe understood it all now. If he was like the chickens, the marmosets, the twins, and another humans in the study, then his infection with Ad-3 6 was helping his body to accumulate fat. He says, What Atkinson and Dhurandhar did for me changed my life. They built everything make sense. It was very liberating and very empowering.

How Does a Virus Lead To Fat?

How would a virus like Ad-3 6 cause fat? Atkinson explains, There are three routes that we believe Ad-3 6 makes people fatter:
( 1) It increases the uptake of glucose from the blood and converts it to fat;( 2) it increases the creation of fat molecules through fatty acid synthase, an enzyme that creates fat; and( 3) it enables the creation of more fat cells to hold all the fat by perpetrating stem cells, which can be transformed into either bone or fat, into fat. So the fat cells that exist are getting bigger, and the body is creating more of them.

The researchers acknowledge that the rooster scratch may have been the start of Randys infection. But they are cautiousthe transmissibility of Ad-3 6 from chickens to humen has never directly been studied.

Though Dhurandhar and Atkinson have conducted several strong studies showing the contribution of Ad-3 6 to fatness, skepticism remains. Atkinson says, I remember dedicating a talk at a seminar where I presented 15 different analyzes in which Ad-3 6 either caused or was correlated to fatness. At the end of it, a good friend said to me, I only dont believe it. He didnt give a reason; he just didnt believe it. People are genuinely stuck on eating and exercising as the only contributors to fatness. But there is more to it.

Dhurandhar adds, Theres a difference between science and religion. What you believe belongs in religion and not in science. In science you have to go by data. I have faced people who are skeptical, but when I ask them why, they cant pinpoint a specific reason. Science is not about belief, it is about fact. There is a sayingIn God we trust, all others bring data.

Reprinted with permission from The Secret Life of Fat by Sylvia Tara. Copyright 2016 by W. W. Norton& Company .

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