Re: Fat Factors

[Guest guest]

I have to say that I would have came, or at least think, of another conclusion:

Given that the RD calculated the nutritional needs to maintain wt......

The formulas that we are using for calculation, no matter which one, are all

estimates, based of what we know today. Needless to say some of the formulas are

70-100 yrs old. How much each one of us " burn " - is very individualized. Its not

one formula fits all, even if the RD used BIA or any other research technologies

to determine intake. Its still has its limitation.

Fat Factors

Colleagues, the following is FYI and does not necessarily reflect my own

opinion. I have no further knowledge of the topic. If you do not wish to

receive these posts, set your email filter to filter out any messages

coming from @nutritionucanlivewith.com and the program will remove

anything coming from me.

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Fat Factors

http://www.nytimes.com/2006/08/13/magazine/13obesity.html?_r=1 & th & emc=th & oref=sl\

ogin<http://www.nytimes.com/2006/08/13/magazine/13obesity.html?_r=1 & th & emc=th & or\

ef=slogin>

By ROBIN MARANTZ HENIG

Published: August 13, 2006

In the 30-plus years that Atkinson has been studying obesity, he

has always maintained that overeating doesn’t really explain it all. His

epiphany came early in his career, when he was a medical fellow at

U.C.L.A. engaged in a study of people who weighed more than 300 pounds

and had come in for obesity surgery. “The general thought at the time

was that fat people ate too much,” Atkinson, now at Virginia

Commonwealth University, told me recently. “And we documented that fat

people do eat too much — our subjects ate an average of 6,700 calories a

day. But what was so impressive to me was the fact that not all fat

people eat too much.”

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!’ ”

The experience with Janet was an early inkling that traditional ideas

about obesity were incomplete. Researchers and public-health officials

have long understood that to maintain a given weight, energy in

(calories consumed) must equal energy out (calories expended). But then

they learned that genes were important, too, and that for some people,

like Janet, this formula was tilted in a direction that led to weight

gain. Since the discovery of the first obesity gene in 1994, scientists

have found about 50 genes involved in obesity. Some of them determine

how individuals lay down fat and metabolize energy stores. Others

regulate how much people want to eat in the first place, how they know

when they’ve had enough and how likely they are to use up calories

through activities ranging from fidgeting to running marathons. People

like Janet, who can get fat on very little fuel, may be genetically

programmed to survive in harsher environments. When the human species

got its start, it was an advantage to be efficient. Today, when food is

plentiful, it is a hazard.

But even as our understanding of genes and behavior has become more

refined, some cases still boggle the mind, like identical twins who eat

roughly the same and yet have vastly different weights. Now a third wave

of obesity researchers are looking for explanations that don’t fall into

the relatively easy ones of genetics, overeating or lack of exercise.

They are investigating what might seem to be the unlikeliest of

culprits: the microorganisms we encounter every day.

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.

If microbes help explain even a small proportion of obesity, that could

shed light on a condition that plagues millions of Americans. Today 30.5

percent of the American public is obese; that is, nearly a third of

Americans have a body-mass index over 30 (which for someone of Janet’s

height is 186 pounds). The Department of Health and Human Services says

obesity may account for 300,000 deaths a year, making it the

second-most-common preventable cause of death after cigarette smoking.

It’s been linked to various diseases: diabetes, high blood pressure,

heart disease, gallbladder disease, sleep apnea, osteoarthritis and some

cancers. “Individuals who are obese,” the department states on its Web

site, “have a 50 to 100 percent increased risk of premature death from

all causes, compared to individuals with a healthy weight.”

If microbes do turn out to be relevant, at least in some cases of

obesity, it could change the way the public thinks about being fat.

Along with the continuing research on the genetics of obesity, the study

of other biological factors could help mitigate the negative stereotypes

of fat people as slothful and gluttonous and somehow less virtuous than

thin people. There is, of course, the risk of overemphasizing how potent

the biological forces are that make some people prone to gaining weight.

Biology sets the context, and that is critical, but obesity still boils

down to whether a person eats too much or exercises enough. The danger

in bending too far in the direction of a biological explanation —

whether that explanation is genetics, infectobesity or some theory yet

to be discovered — is that it could be misinterpreted, by fat and thin

alike, as saying that behavior is irrelevant.

Gordon, whose theory is that obesity is related to intestinal

microorganisms, has never had a weight problem. He’s a rangy man, and

when I met him he was dressed in a plaid shirt and clean chinos

stretching over long, long legs. He wanted to be an astronaut as a kid,

but he was too tall, 6-foot-2 by the time he was a teenager, and he says

that back then, NASA was training only astronauts short enough to

squeeze into the little space capsules of the day. Gordon has a big

friendly face and curly brown hair that make him look younger than 58.

He was a competitive swimmer as a child, from age 9 through his

undergraduate years at Oberlin, but these days he seems more nerd than

athlete: he continually makes puns, for one thing, and he alludes

frequently to “Star Trek.”

“Are you ready to begin our Vulcan mind meld?” he asked when he

collected me at my hotel in St. Louis, where I went to meet him and his

colleagues at the Center for Genome Sciences at Washington University,

which he directs. In a way, I was indeed hoping for a mind meld; I

wanted to find out everything Gordon knows about the bugs in our guts,

and how those bugs might contribute to human physiology — in particular,

how they might make some people fat.

Of the trillions and trillions of cells in a typical human body — at

least 10 times as many cells in a single individual as there are stars

in the Milky Way — only about 1 in 10 is human. The other 90 percent are

microbial. These microbes — a term that encompasses all forms of

microscopic organisms, including bacteria, fungi, protozoa and a form of

life called archaea — exist everywhere. They are found in the ears,

nose, mouth, vagina, anus, as well as every inch of skin, especially the

armpits, the groin and between the toes. The vast majority are in the

gut, which harbors 10 trillion to 100 trillion of them. “Microbes

colonize our body surfaces from the moment of our birth,” Gordon said.

“They are with us throughout our lives, and at the moment of our death

they consume us.”

Known collectively as the gut microflora (or microbiota, a term Gordon

prefers because it derives from the Greek word bios, for “life”), these

microbes have a Star Trek analogue, he says: the Borg Collective, a

community of cybernetically enhanced humanoids with functions so

intertwined that they operate as a single intelligence, sort of like an

ant colony. In its Borglike way, the microflora assumes an extraordinary

array of functions on our behalf — functions that we couldn’t manage on

our own. It helps create the capillaries that line and nourish the

intestines. It produces vitamins, in particular thiamine, pyroxidine and

vitamin K. It provides the enzymes necessary to metabolize cholesterol

and bile acid. It digests complex plant polysaccharides, the fiber found

in grains, fruits and vegetables that would otherwise be indigestible.

And it helps extract calories from the food we eat and helps store those

calories in fat cells for later use — which gives them, in effect, a

role in determining whether our diets will make us fat or thin.

In the womb, humans are free of microbes. Colonization begins during the

journey down the birth canal, which is riddled with bacteria, some of

which make their way onto the newborn’s skin. From that moment on, every

mother’s kiss, every swaddling blanket, carries on it more microbes,

which are introduced into the baby’s system.

By about the age of 2, most of a person’s microbial community is

established, and it looks much like any other person’s microbial

community. But in the same way that it takes only a small percentage of

our genome to make each of us unique, modest differences in our

microflora may make a big difference from one person to another. It’s

not clear what accounts for individual variations. Some guts may be

innately more hospitable to certain microbes, either because of genetics

or because of the mix of microbes already there. Most of the

colonization probably happens in the first few years, which explains why

the microflora fingerprints of adult twins, who shared an intimate

environment (and a mother) in childhood, more closely resemble each

other than they do those of their spouses, with whom they became

intimate later in life.

No one yet knows whether an individual’s microflora community tends to

remain stable for a lifetime, but it is known that certain environmental

changes, like taking antibiotics, can alter it at least temporarily.

Stop the antibiotics, and the microflora seems to bounce back — but it

might not bounce back to exactly what it was before the antibiotics.

In 2004, a group of microbiologists at Stanford University led by

Relman conducted the first census of the gut microflora. It took them a

year to do an analysis of just three healthy subjects, by which time

they had counted 395 species of bacteria. They stopped counting before

the census was complete; Relman has said the real count might be

anywhere from 500 species to a few thousand.

About a year ago, Relman joined with other scientists, including

Gordon, to begin to sequence all the genes of the human gut microflora.

In early June, they published their results in Science: some 78 million

base pairs in all. But even this huge number barely scratches the

surface; the total number of base pairs in the gut microflora might be

100 times that. Because there are so many trillions of microbes in the

gut, the vast majority of the genes that a person carries around are

more microbial than human. “Humans are superorganisms,” the scientists

wrote, “whose metabolism represents an amalgamation of microbial and

human attributes.” They call this amalgamation — human genes plus

microbial genes — the metagenome.

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.

It isn’t clear what the functional significance is of having more

Firmicutes in the gut, nor whether the observed difference is a cause of

the obesity or an effect. But Gordon wanted to see whether something

comparable happened in humans of different weights. Over the past year,

he and his colleagues have evaluated stool samples from 12 obese

patients at a weight-loss clinic at Washington University, along with

some normal-weight controls. They want to see if there’s such a thing as

lean-type and obese-type microflora, and whether weight loss leads to a

change in a person’s microbial community.

Gordon says he is still far from understanding the relationship between

gut microflora and weight gain. “I wish you were writing this article a

year from now, even two years from now,” he told me. “We’re just

beginning to explore this wilderness, finding out who’s there, how does

that population change, which are the key players.” He says it will be a

while before anyone figures out what the gut microbes do, how they

interact with one another and how, or even whether, they play a role in

obesity. And it will be even longer before anyone learns how to change

the microflora in a deliberate way.

You might think a microbial theory of obesity could change people’s

views about the obese, perhaps even lessen the degree to which people

think that obesity is the fat person’s own fault. But anti-fat

sentiments seem to be deeply ingrained and resistant to change, as

reflected in a rather unlikely place: New Scientist, a British magazine.

In an article last year describing the work of Gordon and two groups of

researchers in England who were also investigating the link between

obesity and gut microflora, the author, Bijal Trivedi, was quite

sympathetic to Gordon’s hypothesis. But the article — which is,

remember, about a possible biological cause of obesity — was presented

with a headline that still managed to depict obese people as lazy and

gluttonous. It was called “Slimming for Slackers” and was illustrated

with a fat man in a sweatsuit — the “slacker” of the title — sitting

beside a partly eaten chocolate doughnut, waiting passively for thinness

to arrive.

This is not to single out the New Scientist editors; they are just

reflecting the generalized belief that there’s an element of laziness in

anyone’s obesity. “Gluttony and sloth are two of the seven deadly sins,”

said Ellen Ruppel Shell, author of “The Hungry Gene.” “We ascribe

obesity to a character flaw.” This is what leads to the psychic pain of

being fat, the social isolation of having a condition that everyone

believes to be completely within your control — as if it were a

voluntary purgatory, a case of willfully digging your own grave with

your dinner fork.

I found that this attitude exists even among obese people, including a

woman who was a research subject in Gordon’s clinical study. Joan was

one of the obese patients at Washington University who sent Gordon stool

samples as she lost weight (15 pounds over the course of a year, which

she eventually gained back when she stopped dieting) so they could be

tested for various microbes. She said she hasn’t been curious enough to

try to find out about her microflora; she’s too busy, and besides, she

already knows where to place the blame for her excess weight — not on a

microbe but on herself. “I know that I’m not being obedient, I’m not

using my body the way God intended,” said Joan, who asked me to refer to

her only by her middle name. “I know how I’m supposed to eat, but I’m

not having a healthy appetite, you know what I’m saying? I’m not wanting

to be obedient.”

But it’s not about obedience — or at least not only about obedience.

“The biochemistry of the body of the obese person is very different from

that of a lean person,” said Atkinson, Janet S.’s former

physician. “If the obese person gets down to a lean person’s weight,

their biochemistry is not the same.” Losing weight is hard, keeping it

off is harder and, especially for some unfortunate souls, the body seems

to work against itself in the struggle.

There’s another way that biological middlemen might be involved in

obesity — in this case, not the gut microbes (mostly bacteria) with

which we co-exist but the viruses and other pathogens that occasionally

infect us and make us ill. This is the subspecialty that is being called

infectobesity.

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.

The findings violated three pieces of conventional wisdom, Dhurandhar

said recently: “The first is that viruses don’t cause obesity. The

second is that obesity leads to high cholesterol and triglycerides. The

third is that avian viruses don’t infect humans.”

Dhurandhar, now 46, is a thoughtful man with a head of still-dark hair.

Like Gordon, he has never been fat. But even though he is so firmly in

the biological camp of obesity researchers, he ascribes his own weight

control to behavior, not microbes; he says he is slim because he walks

five miles a day, lifts weights and is careful about what he eats. Being

overweight runs in his family; Dhurandhar’s father, who still practices

medicine in India, began treating obese patients because of his own

struggle to keep his weight down, from a onetime high of 220.

Slim as he is, Dhurandhar nonetheless is sensitive to the pain of being

fat and the maddening frustration of trying to do anything about it. He

takes to heart the anguished letters and e-mail he receives each time

his research is publicized. Once, he said, he heard from a woman whose

10-year-old grandson weighed 184 pounds. The boy rode his bicycle until

his feet bled, hoping to lose weight; he was so embarrassed by his body

that he kept his T-shirt on when he went swimming. The grandmother told

Dhurandhar that the virus research sounded like the answer to her

prayers. But the scientist knew that even if a virus was to blame for

this boy’s obesity, he was a long way from offering any real help.

In 1992, Dhurandhar moved his wife and 7-year-old son to the United

States in search of a lab where he could continue his research. At

first, because infectobesity was so far out of the mainstream, all he

could find was unrelated work at North Dakota State University. “My wife

and I gave ourselves two years,” he recalled. “If I didn’t find work in

the field of viruses and obesity in two years, we would go back to Bombay.”

Dhurandhar’s battle against the conventional wisdom was reminiscent of

the struggle a decade earlier of two Australian scientists, who were

also proposing an infectious cause for a chronic disease, in their case,

a bacterium that causes ulcers. The Australians were met with skepticism

at first, but eventually they accumulated enough evidence to make it

hard to ignore the connection between ulcers and the bacterium,

Helicobacter pylori. It helped that one of them, Barry J. Marshall,

dramatically swallowed a pure culture of H. pylori — and promptly came

down with symptoms of gastritis, the first stage of an ulcer. (The H.

pylori story ended with the ultimate vindication: Marshall and his

collaborator, J. Robin Warren, won the Nobel Prize in 2005.)

One month before his self-imposed deadline in 1994, Dhurandhar received

a job offer from 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.

Were fat people just more prone to infection? Probably not, because the

scientists also screened for antibodies to two other strains of

adenovirus, and there was no difference between those who were obese and

those who were not. Could the differences be explained by genes instead

of by viruses? Probably not, because the scientists controlled for genes

in a follow-up study that involved 90 pairs of twins. In the twin study,

they found 20 identical-twin pairs who were “discordant” for antibodies

to Ad-36, meaning one twin had been exposed to the virus and the other

twin had not. In the discordant pairs, the infected twin tended to be

fatter, with an average of almost 2 percent more body fat (29.6 percent

versus 27.5 percent) than the uninfected twin — even though they shared

exactly the same genes.

If Ad-36 is a cause of obesity, Atkinson says, you’re more likely to

catch it from a newly infected and still-contagious thin person than

from someone who has already gained weight because of its effects.

Exactly what the virus does to create this kind of long-term

perturbation is still being investigated. In a paper published last year

in The International Journal of Obesity, Atkinson and Dhurandhar, along

with five of their colleagues, presented evidence for how Ad-36 might

affect fat cells directly, “leading to an increased fat-cell number and

increased fat-cell size.”

As for the other pathogens implicated in infectobesity — nine in all —

certain viruses are known to impair the brain’s appetite-control

mechanism in the hypothalamus, as happens in some cases of people

becoming grossly obese after meningitis. Scientists also point to a

commonality between fat cells and immune-system cells, although the

exact significance of the connection is unclear. Immature fat cells, for

instance, have been shown to behave like macrophages, the immune cells

that engulf and destroy invading pathogens. Mature fat cells secrete

hormones that stimulate the production of macrophages as well as another

kind of immune-system cell, T-lymphocytes.

Another line of investigation in the field of infectobesity concerns

inflammation, a corollary of infection. Obese people have higher levels

of two proteins related to inflammation, C-reactive protein and

interleukin-6. This may suggest that an infectious agent has set off

some sort of derangement in the body’s system of fat regulation, making

the infected person fat. A different interpretation is not about obesity

causation but about its associated risks. Some scientists, including

Gordon’s colleagues at Washington University, are trying to see

whether the ailments of obesity (especially diabetes and high blood

pressure) might be caused not by the added weight per se, but by the

associated inflammation.

Infectobesity has its critics, among them Bloom, a researcher at

Imperial College London. Bloom said that if he were working at a

research agency, he’d give money for studies into the viral causes of

obesity, just in case there’s something there. But he said he wouldn’t

put the theory into a medical-school textbook just yet. His main

objection, he said, is that “I don’t think we need that explanation,

since we have a perfectly good other explanation.” Like Dhurandhar and

Atkinson, Bloom suspects that obesity has a biological cause — but

rather than turning to gut microflora or adenovirus infection for an

explanation, he is partial to what he calls “the lazy-greedy gene”

hypothesis, his slightly disparaging shorthand for what is more

generally known as the thrifty genotype.

The thrifty-genotype hypothesis holds that there was, once upon a time,

an adaptive advantage to being able to get fat. Our ancestors survived

unpredictable cycles of food catastrophes by laying down fat stores when

food was plentiful, and using up the stores slowly when food was scarce.

The ones who did this best were the ones most likely to survive and to

pass on the thrifty genotype to the next generation. But this mechanism

evolved to get through a difficult winter — and we’re living now in an

eternal spring. With food so readily available, thriftiness is a

liability, and the ability to slow down metabolism during periods of

reduced eating (a k a dieting) tends to create a fatter populace, albeit

a more famine-proof one.

Bloom, by the way, does not give much credence to Dhurandhar’s analogy

between the Ad-36-obesity connection and the recent history of H. pylori

and ulcers — even though each started out looking like just another

wacky idea. “There are so many crazy theories,” he said. “But just

because one in a hundred turns out to be correct doesn’t mean all the

crazy theories are correct.”

Obesity has turned out to be a daunting foe. Many of us are tethered to

bodies that sabotage us in our struggle to keep from getting fat, or to

slim down when we do. Microbes might be one explanation. There might be

others, as outlined in June in a paper in The International Journal of

Obesity listing 10 “putative contributors” to obesity, among them sleep

deprivation, the increased use of psychoactive prescription drugs and

the spread of air-conditioning.

But where does this leave us, exactly? Whatever the reason for any one

individual’s tendency to gain weight, the only way to lose the weight is

to eat less and exercise more. Behavioral interventions are all we’ve

got right now. Even the supposedly biological approach to weight loss —

that is, diet drugs — still works (or, more often, fails to work) by

affecting eating behavior, through chemicals instead of through

willpower. If it turns out that microbes are implicated in obesity, this

biological approach will become more direct, in the form of an antiviral

agent or a microbial supplement. But the truth is, this isn’t going to

happen any time soon.

On an individual level and for the foreseeable future, if you want to

lose weight, you still have to fiddle with the energy equation. Weight

still boils down to the balance between how much a particular body needs

to maintain a certain weight and how much it is fed. What complicates

things is that in some people, for reasons still not fully understood,

what their bodies need is set unfairly low. It could be genes; it could

be microbes; it could be something else entirely.

Janet S. is one such person. Thirty years after her obesity surgery, 170

pounds lighter than when she started, she still needs to restrict her

food intake to keep from gaining it all back.

“I definitely have to diet — damn it, I should have a pass on that,

don’t you think?” said Janet, now 55, a human-resources administrator in

Southern California, married and with a teenage daughter who is tall and

slender. Even with the surgery, and even maintaining a weight that is

borderline obese (at least according to the government definition; Janet

weighs 180 pounds, plus or minus 15, meaning her body-mass index hovers

around the magic number of 30), she can never enjoy food with complete

and carefree abandon.

This is typical of people who have lost weight — not only a lot of

weight, as Janet has, but even a little weight. According to Rudolph

Leibel, an obesity researcher at Columbia University who was involved in

the discovery of the first human gene implicated in obesity, if you take

two nonobese people of the same weight, they will require different

amounts of food depending on whether or not they were once obese. It

goes in precisely the maddening direction you might expect: formerly fat

people need to eat less than never-fat people to maintain exactly the

same weight. In other words, a 150-pound woman who has always weighed

150 might be able to get away with eating, say, 2,500 calories a day,

but a 150-pound woman who once weighed more — 20 pounds more, 200 pounds

more, the exact amount doesn’t matter — would have to consume about 15

percent fewer calories to keep from regaining the weight. The change

occurs as soon as the person starts reducing, Leibel said, and it “is

not proportional to amount of weight lost, and persists over time.”

For many people, then, losing weight and keeping the weight off requires

a constant state of hunger — and when you’re hungry, you’re miserable.

You think of nothing but food every moment of the day. All morning you

think about lunch, all afternoon you think about dinner, and when you’re

asleep, you dream of food.

Or, as Judith put it in her memoir, “Fat Girl”: “Some people

daydream heroic deeds or sex scenes or tropical vacations. I daydream

crab legs dipped in hot butter.” She wrote about fellow warriors who,

like her, struggle to keep off the weight they worked so hard to lose.

As they approach the all-you-can-eat buffet, she wrote, “they square

their shoulders. They ready for combat with Virginia baked ham,

sweet-potato soufflé and those puffy dinner rolls with butter and a

three-layer chocolate mousse cake. Food is the enemy. Food is also the

mother, the father, the warmhearted lover, the house built of redbrick

that not even the wolf can blow down.”

Current public-health messages deny this harsh reality. They make losing

weight sound easy, just a simple matter of doing the math and applying

some willpower. A pound of fat contains 3,500 calories, government

documents say, and if you cut down a week’s worth of food intake or

increase exercise by a total of 3,500 calories, then, voilà — you lose a

pound. “To lose weight, you must use more energy than you take in,”

states the Web site of the Office of the Surgeon General. “A difference

of one 12-oz. soda (150 calories) or 30 minutes of brisk walking most

days can add or subtract approximately 10 pounds to your weight each year.”

But if genes or viral infection or gut microflora are involved, then for

some people 3,500 calories might not equal a pound of fat, and 150 fewer

calories a day might not mean they’ll lose 10 pounds in a year. As

scientists continue to investigate how obese people are different, we

can only hope that a side benefit will be a more largehearted

understanding of what it means to be fat and how hard it is to try to

become, and to remain, less fat.

A more concrete benefit would be to develop ways to interfere with the

action of the offending microbes. Atkinson, for one, foresees a day when

Ad-36 antibody screening becomes as routine as cholesterol screening. He

has a financial stake in making this happen; when he moved to Virginia

two years ago, he started a company called Obetech to market his Ad-36

antibody test, for which he charges $450. But he said he has an

altruistic motive as well. The people most likely to benefit from such

testing, he said, are not fat people but thin people, whose infections

are so recent that they haven’t yet begun to gain weight. But they are

the least likely to pay to have it done without it being part of a

routine checkup.

Based on animal studies, Atkinson assumes that people infected with

Ad-36 have a better than even chance of becoming obese. “But if they

watch their diet, and if they exercise, they can avoid it.” Further in

the future, he said, there might be a way to administer antiviral drugs

to infected individuals early enough to block the effect of Ad-36 on the

fat cells.

Gordon, too, is hoping that his research will eventually lead to new

strategies for treating obesity. It’s a long way off, he said, but it’s

the beacon that keeps him and his colleagues working.

“How can you manipulate the microbial community to more broadly affect

energy balance?” he asked, enumerating the research questions still to

be tackled. “Can one size fit all, or can you match nutrition to the

microbes in your gut?” After obese-type microflora are differentiated

from lean-type, Gordon said, the next step would be what he calls

“personalized nutrition” — matching diet to the digestive properties of

each person’s unique microflora.

Such deliberate manipulation of the gut microflora is a long way off —

years and years off, according to Gordon — but its possibility “is what

this first phase of our work is underscoring, and we hope it will turn

out to be an important tool in the fight against obesity.”

Robin Marantz Henig is a contributing writer to the magazine. Her last

cover article was about the science of lie detection.

--

ne Holden, MS, RD <

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