Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Infectious obesity

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I posted on AD36, the fat virus, a while ago.

The below quotes are from an article from the NY Times entitled “Fat Factors“. To read the NY times article, you have to register. Try the username/pw bugmenot/bugmenot if you’d rather avoid that.

Here are some excerpts:

One of Atkinson’s most memorable patients was Janet S., a bright, funny 25-year-old who weighed 348 pounds when she finally made her way to U.C.L.A. in 1975. In exchange for agreeing to be hospitalized for three months so scientists could study them, Janet and the other obese research subjects (30 in all) each received a free intestinal bypass. During the three months of presurgical study, the dietitian on the research team calculated how many calories it should take for a 5-foot-6-inch woman like Janet to maintain a weight of 348. They fed her exactly that many calories — no more, no less. She dutifully ate what she was told, and she gained 12 pounds in two weeks — almost a pound a day.

“I don’t think I’d ever gained that much weight that quickly,” recalled Janet, who asked me not to use her full name because she didn’t want people to know how fat she had once been. The doctors accused her of sneaking snacks into the hospital. “But I told them, ‘I’m gaining weight because you’re feeding me a tremendous amount of food!’ ”

[…]

One year ago, the idea that microbes might cause obesity gained a foothold when the Pennington Biomedical Research Center in Louisiana created the nation’s first department of viruses and obesity. It is headed by Nikhil Dhurandhar, a physician who invented the term “infectobesity” to describe the emerging field. Dhurandhar’s particular interest is in the relationship between obesity and a common virus, the adenovirus. Other scientists, led by a group of microbiologists at Washington University in St. Louis, are looking at the actions of the trillions of microbes that live in everyone’s gut, to see whether certain intestinal microbes may be making their hosts fat.

[…]

Gordon first began studying the connection between the microflora and obesity when he saw what happened to mice without any microbes at all. These germ-free mice, reared in sterile isolators in Gordon’s lab, had 60 percent less fat than ordinary mice. Although they ate voraciously, usually about 30 percent more food than the others, they stayed lean. Without gut microbes, they were unable to extract calories from some of the types of food they ate, which passed through their bodies without being either used or converted to fat.

When Gordon’s postdoctoral researcher Fredrik Bäckhed transplanted gut microbes from normal mice into the germ-free mice, the germ-free mice started metabolizing their food better, extracting calories efficiently and laying down fat to store for later use. Within two weeks, they were just as fat as ordinary mice. Bäckhed and Gordon found at least one mechanism that helps explain this observation. As they reported in the Proceedings of the National Academy of Sciences in 2004, some common gut bacteria, including B. theta, suppress the protein FIAF, which ordinarily prevents the body from storing fat. By suppressing FIAF, B. theta allows fat deposition to increase. A different gut microbe, M. smithii, was later found to interact with B. theta in a way that extracts additional calories from polysaccharides in the diet, further increasing the amount of fat available to be deposited after the mouse eats a meal. Mice whose guts were colonized with both B. theta and M. smithii — as usually happens in humans in the real world — were found to have about 13 percent more body fat than mice colonized by just one or the other.

Gordon likes to explain his hypothesis of what gut microbes do by talking about Cheerios. The cereal box says that a one-cup serving contains 110 calories. But it may be that not everyone will extract 110 calories from a cup of Cheerios. Some may extract more, some less, depending on the particular combination of microbes in their guts. “A diet has a certain amount of absolute energy,” he said. “But the amount that can be extracted from that diet may vary between individuals — not in a huge way, but if the energy balance is affected by just a few calories a day, over time that can make a big difference in body weight.”

In another line of research, Gordon and his postdoctoral researcher Ruth Ley compared the microflora in two kinds of mice: normal-weight mice and mice with a genetic mutation that made them fat. Like humans, the mice had microflora consisting almost exclusively of two divisions of bacteria, the Bacteroidetes and the Firmicutes. But the proportions differed depending on whether the host was thin or fat. The normal-weight mice had more Bacteroidetes than Firmicutes in their gut microflora. The genetically obese mice had the opposite proportions: 50 percent fewer Bacteroidetes, 50 percent more Firmicutes.

[…]

The idea of infectobesity dates to 1988, when Nikhil Dhurandhar was a young physician studying for his doctorate in biochemistry at the University of Bombay. He was having tea with his father, also a physician and the head of an obesity clinic, and an old family friend, S. M. Ajinkya, a pathologist at Bombay Veterinary College. Ajinkya was describing a plague that was killing thousands of chickens throughout India, caused by a new poultry virus that he had discovered and named with his own and a colleague’s initials, SMAM-1. On autopsy, the vet said, chickens infected with SMAM-1 revealed pale and enlarged livers and kidneys, an atrophied thymus and excess fat in the abdomen.

The finding of abdominal fat intrigued Dhurandhar. “If a chicken died of infection, having wasted away, it should be less fat, not more,” he remembered thinking at the time. He asked permission to conduct a small experiment at the vet school.

Working with about 20 chickens, Dhurandhar, then 28, infected half of them with SMAM-1. He fed them all the same amount of food, but only the infected chickens became obese. Strangely, despite their excess fat, the infected obese chickens had low levels of cholesterol and triglycerides in their blood — just the opposite of what was thought to happen in humans, whose cholesterol and triglyceride levels generally increase as their weight increases. After his pilot study in 1988, Dhurandhar conducted a larger one with 100 chickens. It confirmed his finding that SMAM-1 caused obesity in chickens.

But what about humans? With a built-in patient population from his clinic, Dhurandhar collected blood samples from 52 overweight patients. Ten of them, nearly 20 percent, showed antibody evidence of prior exposure to the SMAM-1 virus, which was a chicken virus not previously thought to have infected humans. Moreover, the once-infected patients weighed an average of 33 pounds more than those who were never infected and, most surprisingly, had lower cholesterol and triglyceride levels — the same paradoxical finding as in the chickens.

[…]

One month before his self-imposed deadline in 1994, Dhurandhar received a job offer from Richard Atkinson, who was then at the University of Wisconsin, Madison. Atkinson, always on the lookout for new biological explanations of obesity, wanted to collaborate with Dhurandhar on SMAM-1. But the virus existed only in India, and the U.S. government would not allow it to be imported. So the scientists decided to work with a closely related virus, a human adenovirus. They opened the catalogue of a laboratory-supply company to see which one of the 50 human adenoviruses they should order.

“I’d like to say we chose the virus out of some wisdom, out of some belief that it was similar in important ways to SMAM-1,” Dhurandhar said. But really, he admitted, it was dumb luck that the adenovirus they started with, Ad-36, turned out to be so fattening.

By this time, several pathogens had already been shown to cause obesity in laboratory animals. With Ad-36, Dhurandhar and Atkinson began by squirting the virus up the nostrils of a series of lab animals — chickens, rats, marmosets — and in every species the infected animals got fat.

“The marmosets were most dramatic,” Atkinson recalled. By seven months after infection, he said, 100 percent of them became obese. Subsequently, Atkinson’s group and another in England conducted similar research using other strains of human adenovirus. The British group found that one strain, Ad-5, caused obesity in mice; the Wisconsin group found the same thing with Ad-37 and chickens. Two other strains, Ad-2 and Ad-31, failed to cause obesity.

In 2004, Atkinson and Dhurandhar were ready to move to humans. All of the 50 strains of human adenoviruses cause infections that are usually mild and transient, the kind that people pass off as a cold, a stomach bug or pink eye. The symptoms are so minor that people who have been infected often don’t remember ever having been sick. Even with such an innocuous virus, it would be unethical, of course, for a scientist to infect a human deliberately just to see if the person gets fat. Human studies are, therefore, always retrospective, a hunt for antibodies that would signal the presence of an infectious agent at some point in the past. To carry out this research, Atkinson developed — and patented — a screening test to look for the presence of Ad-36 antibodies in the blood.

The scientists found 502 volunteers from Wisconsin, Florida and New York willing to be screened for antibodies, 360 of them obese and 142 of them of not obese. Of the leaner subjects, 11 percent had antibodies to Ad-36, indicating an infection at some point in the past. (Ad-36 was identified relatively recently, in 1978.) Among the obese subjects, 30 percent had antibodies— a difference large enough to suggest it was not just chance. In addition, subjects who were antibody-positive weighed significantly more than subjects who were uninfected. Those who were antibody-positive also had cholesterol and triglyceride readings that were significantly lower than people who were antibody-negative — just as in the infected chickens — a finding that held true whether or not they were obese. Fat Factors

A calorie is not a calorie: anyone who says otherwise is ignoring the second law of thermodynamics.

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Written by alienrobotgirl

31 August, 2006 at 4:11 pm

One Response

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  1. […] metabolism, that a calorie is not always a calorie. I have posted on AD-36, the fat virus, and infectious obesity, a couple of times before. Some of the theories I have previously thrown into the field about what […]


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