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Expanding Guts in Pythons and People

Regular readers of this blog might remember a post I wrote a few months ago about weight-loss surgery. A mouse study suggested that surgery works — triggering weight loss and, often, diabetes remission — not because it makes the stomach smaller, but because it drastically changes its biochemistry.

I took a close look at that study and a slew of others in a feature published in today’s issue of Nature. Rodent models have shown that after surgery, the gut goes through many dramatic changes. Bacterial compositions shift, for example, bile acids flow more freely, and the intestines swell.

That last bit maybe isn’t so surprising — after all, once the stomach shrinks to the size of an egg, suddenly a whole lot more undigested food is going to hit the intestines than before. But what is surprising, as Nicholas Stylopoulos’s group published last year in Science, is that this abrupt growth seems to trigger a host of permanent metabolic changes in the gut.

As I explain in the feature:

“The rapid growth requires a lot of energy, which comes from glucose. Glucose uptake by the changing organ increases, and the change is maintained over time, Stylopoulos says. ‘Essentially, the intestine becomes a bigger and a more hungry organ that needs more glucose than before.’

Stylopoulos believes that this tissue growth in the gut is the main driver of the surgery’s remarkable metabolic benefits — not a reduction in calorie intake.”

A couple of weeks ago, while I was doing the final fact-checks for the feature, Stylopoulos told me a fun tidbit about how the same sort of change has been reported in….wait for it….Burmese Pythons. “They have some amazing similarities,” he said.

Unlike most mammals, which eat small meals several times a day, pythons engulf enormous meals — ranging from .25 to 1.6 times their own body mass — many months apart. As biologists Stephen Secor and Jared Diamond pointed out in a 1998 Nature paper, that would be equivalent to a 136-pound person swallowing a 220-pound meal “in one gulp.”

After it has finished its meal, a python curls up for 5 to 11 days to digest it. “They have this amazing capacity to increase the length and the overall mass of their intestines within hours,” Stylopoulos told me. Once digestion is complete, their gut goes back to normal.

Stephen Secor, J. Exp. Biol. 2008 (Python intestines; DPF = days post feeding)

So the python gut expands rapidly after eating, just as Stylopoulos showed happens in the rat gut after bypass surgery. But “what is really amazing,” Stylopoulos said, is that the python gut also sees a surge in glucose metabolism after being fed.

Here’s an image from one of Sekor’s later studies, showing glucose levels (red and yellow) in a hungry animal (top) versus a just-fed one (bottom):

The difference between the python model and the bariatric surgery model is that for pythons, the gut goes back to normal once the food is gone. With surgically treated rats, in contrast, the gut expansion doesn’t seem to go away, presumably because the undigested food keeps on coming.

That said, Stylopoulos’s study found that the post-surgery gut doesn’t grow forever. Over time, it reaches a plateau and so does its glucose metabolism. That could be why some people who see initial metabolic benefits after bariatric surgery ultimately regress back into diabetes.

But as I mentioned, the gut expansion is just one of many things that happen after bariatric surgery. To learn about the others, head over to Nature.

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Obesity Researchers Have Been Looking At The Wrong Gene

If you were investigating a crime scene, you wouldn’t just accuse the nearest bystander. The real culprit could be miles away.

In 2007, a team of British researchers announced that genetic variants within the FTO gene could predispose people to being fat. On average, people with one set of these variants weighed 1.6 kilograms more than people with none, and those with two sets—including one in six Europeans—weighed 3 kilograms more.

It was an important discovery. By studying twins, scientists had already shown that obesity runs in families, to an extent that can’t be explained by a shared environment. It was clear that some genes can influence how much we weigh (though, obviously, not exclusively*), but no one had identified any of them. FTO was the first. The media, as is their unfortunate wont, labelled it a “fat gene”.

Many later studies corroborated FTO’s connection to body weight. When scientists deleted the gene in mice, the rodents grew up thinner. When they switched the gene on, over and above its usual activity, mice ate more and put on weight. The pieces seemed to fit.

But right from the start, FTO was shrouded in mystery. No one really knew what the gene did, nor how it could influence our weight. And some parts of the FTO story just didn’t make sense.

When genes are switched on (scientists say “expressed”), the information in their DNA is converted into a related molecule called RNA. These RNA transcripts are then used to make proteins. But changes in FTO that were linked to obesity all cluster in a tiny part of the gene that doesn’t code for proteins at all—it gets cut out at the RNA stage.

Stranger still, these obesity-related changes didn’t seem to affect anything about FTO itself. They didn’t influence the way the gene is expressed, or the protein that it makes. And when scientists identified mutations in FTO that do impair its protein or change its expression, none of these were linked to obesity!

Now, Marcelo Nobrega from the University of Chicago thinks he has solved the mystery. His team have found that the obesity-linked bits of FTO reach across to a distant part of the genome to control another gene called IRX3. And it’s IRX3 that changes the levels of fat in the body.

Many scientists have fixated on FTO and tried to puzzle out what it does and how it affects body weight. These new results suggest that they have been looking at the wrong gene.

Nobrega’s team—primarily Scott Smemo, Juan Tena and Kyoung-Han Kim—used a technique that tests for physical contacts between different parts of the genome. Remember that the genome isn’t just a string of As, Gs, Cs, and Ts on a page—it’s a physical thing. It is made of DNA that twists and loops into three-dimensional spaghetti-like whorl, turning distant bits into close neighbours.

The team found that one such long-range connection between the obesity-related part of FTO and the region that switches on IRX3. The two regions were linked in mice, in zebrafish, and in human cells, which shows that the they have been interacting for at least 400 million years. And the team showed that the obesity-related FTO variants all change the activity of IRX3 in the human brain, and specifically in areas like the hypothalamus that control our metabolism and how much we eat.

What does IRX3 do? To find out, Nobrega’s team deleted the gene in mice. The results were stark. The animals grew up to be 25 to 30 percent lighter than typical rodents, and had much less body fat. They metabolism was higher because they tended to form calorie-burning brown fat rather than the energy-storing white fat. And they could seemingly eat with impunity; even on a high-fat diet, they didn’t put on weight.

So, it seems that a small part of FTO affects body weight by affecting IRX3 rather than FTO itself. Presumably, some variants in this region switch on IRX3 to an extreme degree and this hyperactive gene changes many aspects of our metabolism, making individuals more likely to pile on the pounds.

The details are still hazy, and the team is busy trying to clarify them. “We’ve made mice that make too much IRX3 in the brain,” says Nobrega, “and we’re hoping that they will become fat. Then we can see what’s different what’s different about them, whether it’s their appetite or other behavioural things.”

But wait a minute: what about those early studies showing that deleting FTO makes mice thinner? Nobrega thinks that these results were deceptive. “The mice didn’t just lose fat but also muscle and limb mass,” he says. Losing the gene didn’t produce a straight “anti-obesity” effect, but people were inclined to view it as such because of their biases.

What’s more, Nobrega’s team looked up the details of over 7,500 strains of mice that were missing specific genes, and found that almost a third of them had noticeable differences in size or weight! The FTO-less mice weren’t special. People interpreted their traits—their ‘phenotype—in the context of obesity because they were expecting an effect of that kind.

“I’ve been doing mouse genetics for many years,” says Nobrega. “There are some phenotypes that are very specific. There aren’t very many genes that will lead to retinitis pigmentosa if you knock them out. But bodyweight is very different. All types of things can make your bodyweight fluctuate. We should have been more careful about making interpretations about what this phenotype meant.”

Philippe Froguel from Imperial College London, one of the pioneers who first showed the link between FTO and obesity, is convinced by the new results. “From the beginning we were slightly suspicious,” he says. “I have been never impressed by the numerous papers published about FTO.”

Mark McCarthy from the University of Oxford, who also led one of the studies that brought FTO into the limelight, agrees. “It’s a timely reminder that when contemplating the scene of a crime, it is wise to look beyond those potential culprits standing nearest to the body, some of whom may well be innocent bystanders, and to look for ‘motive’ amongst those who may be standing a little distance away,” he says.

Nobrega thinks that these lessons probably apply to many other genes. The vast majority of genome-wide association studies, which look for genetic variations linked to traits and diseases, have identified variants in regions that don’t code for proteins—just like the obesity-related ones in FTO. And just as in FTO, scientists often assume that these variants affect the gene that they sit inside when they could actually be affecting one a long way away. “They’re investing in those genes and doing work on them without doing their due diligence.”

Reference: Smemo, Tena, Kim, Gamazon, Sakabe, Gomez-Marin, Aneas, Credidio, Sobreira, Wasserman, Lee, Puviindran, Tam, Shen, Son, Vakili, Sung, Naranjo, Acemel, Manzanares, Nagy, Cox, Hui, Gomez-Skarmeta & Nobrega. 2014. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature http://dx.doi.org/10.1038/nature13138

* A word of caution: despite what the media always implies when discussing the genetics of obesity, discovering an obesity-related gene does not mean that obesity is “in the genes” or that it’s something out of our control. Obesity is a complex condition with many underlying influences, including diet, activity, cultural norms, the environment we live in, media messages, our gut bacteria, and dozens more. Genes are part of this complex tapestry. They’re not deterministic—having an obesity-related variant doesn’t destine you to becoming fat. They don’t work in isolation from the environment but in tandem with it—they might affect our responses to food, or the way we process the calories we eat. It’s a case of nature via nurture. More on this here.


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The Mucus-Lover that Stops Mice from Getting Fat

When Bob Paine chucked starfish into the Pacific Ocean in 1963, he was also throwing bombs into the heart of ecology. Back then, the prevailing view was that communities of animals and plants were fairly stable, provided that they contained a diverse set of members. But Paine showed that some species are disproportionately influential. Take the ochre starfish. When Paine prised them from a stretch of Washington shore and pitched them into the surf, the mussels that the starfish ate advanced over the shore like a black glacier. They crowded out other creatures and radically remodelled the coastline.

Paine described crucial species like the starfish as “keystones”, after the central stone that stops an arch from collapsing. The whole community matters but some species are particularly important. Or to borrow from Orwell, “All animals are equal, but some animals are more equal than others”.

Now, the same lessons are being learnt in an ecosystem that’s very different to the rocky Pacific coast—the intestine. The guts of humans and other mammals contain thriving trillions of bacteria and other microbes. This “microbiota” outnumbers the cells that make up our actual bodies. They are so numerous that they are usually studied en masse. Scientists collect samples—say, from faeces—and sequence all the DNA within them, piecing together the identities of the resident species and families.

It’s a powerful approach, which has already taught us much about our gut passengers. Studies have show how these communities change as we get grow older, eat different diets, or take courses of antibiotics. Unsavoury but impressive studies have shown that people can be cured of life-threatening gut infections by being implanted with someone else’s faeces. And many scientists have found links between our gut bacteria and obesity.

For example, in 2007, Ruth Ley, Peter Turnbaugh and Jeffrey Gordon showed that a group of bacteria called the Bacteroidetes are rarer in the guts of obese mice and humans, while a rival group—the Firmicutes—are more common. And a few months ago, Turnbaugh and Lee Kaplan showed that gastric bypass surgery (at least, in mice) might lead to weight loss because it changes an individual’s gut microbe society. Antibiotics might lead to obesity by creating similar upheavals.

The whole community matters but, again, some species are particularly important. One of these Very Important Prokaryotes is called Akkermansia muciniphila. Willem de Vos from Waginingen University first discovered it in 2004 but humans have been carrying it for much longer. Akkermansia accounts for 3 to 5 percent of the bacteria in a normal gut, making it one of our more common intestinal microbes. And it seems to wield a strong influence on our body weight.

Amandine Everard and Patrice Cani from the Catholic University of Louvain have been working with de Vos to understand how this microbe gives its host the guts to stave off the pounds.

They found that Akkermansia is 3,300 times less common in the guts of mice that are genetically predisposed to being obese than in normal rodents. Also, its numbers fall by 100 times when any mouse eats a high-fat diet. This mirrors the results of surveys in humans—if people have lots of Akkermansia in their guts, they tend to be slimmer.

But boost the microbe’s faltering numbers, and you can reverse several of the problems associated with obesity. When team fed their mice with a dose of Akkermansia, they put on less weight and body fat after eating a high-fat diet. They also showed fewer signs of type 2 diabetes. For example, their climbing levels of sugar in their blood completely reversed, and they became less resistant to insulin—the hormone that controls blood sugar.

When the team fed their mice with dead bacteria, nothing happened, proving that the bacteria need to be alive to exert their weight-controlling influence. They don’t, however, need any help. Everard found that a high-fat diet changes the entire community of bacteria in a mouse’s gut, but the addition of Akkermansia doesn’t. Whatever it does, it does it by itself. The whole community matters but some species are particularly important.

Akkermansia feeds upon the delectable mucus that covers our intestines—its species name, muciniphila, is Latin for “mucus lover”. This mucus comes in two layers. The inner one is a barrier that keeps harmful microbes out. The outer one is a meeting room, where our cells parlay with helpful species like Akkermansia.

As mice gain weight, their mucus layer gets thinner, but Akkermansia seems to prevent this erosion. By shoring up the mucus, it could prevent other microbes from inflaming the gut and triggering other changes that cause disease. And there’s probably more. Everard’s team also found evidence that Akkermansia could also affect the division of its host’s gut cells. It also persuades its host to release molecules that kill competing bacteria and reduce inflammation.

Cani sees the relationship between the microbe and its host as a mutually beneficial one. “The host provides energy and a habitat to Akkermansia and, in turn, Akkermansia protects its host from invading microbes.”

Akkermansia might eventually help us to control our weight or reduce the risk of diabetes, but that will take a lot more research. This study was done in mice, and Cani wants to check that the same relationships happen in the human gut. But since this microbe actually lives inside the mucus layer, it has a lot more potential for affecting our bodies than a lot of other “probiotics”. Indeed, when Everard’s team repeated their experiments with Lactobacillus plantarum—a “helpful” microbe commonly used in probiotic foods—it did nothing for the fat mice.

This is a reminder that our gut bacteria are not stowaways. They’re an intimate part of our lives. They contribute to the huge network of proteins and hormones that controls how hungry we get when we don’t eat or how full we feel when we do. They affect how much fat we store and how much sugar builds up in our blood. They influence our immune system, and how we decide which microbes to tolerate and which to attack.

We’re only starting to understand the conversations that happen between our guts and the microbes within them. And we’re only starting to identify the most important species among the vast hordes—the gut equivalents of Paine’s starfish. Rob Knight from the University of Boulder in Colorado, who studies the microbiota, thinks that research in the future will “likely shift back and forth between studies of individual microbes, like this one, and whole-community studies that allow us to generate hypotheses about which other key players in the gut they interact with.”

Reference: Everard, Belzer, Geurts, Ouwerkerk, Druart, Bindels, Guiot, Derrien, Muccioli, Delzenne, de Vos & Cani. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.

More on gut bacteria:

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Antibiotics fuel obesity by creating microbe upheavals

We aren’t single individuals, but colonies of trillions. Our bodies, and our guts in particular, are home to vast swarms of bacteria and other microbes. This “microbiota” helps us to harvest energy from our food by breaking down the complex molecules that our own cells cannot cope with. They build vitamins that we cannot manufacture. They ‘talk to’ our immune system to ensure that it develops correctly, and they prevent invasions from other more harmful microbes. They’re our partners in life.

What happens when we kill them?

Farmers have been doing that experiment in animals for more than 50 years. By feeding low doses of antibiotics to healthy farm animals, they’ve found that they could fatten up their livestock by as much as 15 percent. You can put the antibiotics in their feed or in their water. You can give the drugs to cows, sheep, pigs or chickens. You can try penicillins, or tetracyclines, or many other classes of antibiotics. The effect is the same: more weight.

Consistent though this effect is, no one really understands why it works. The safe bet is that the drugs are exerting their influence by killing off some of the microbiota. Now, Ilseung Cho from the New York University School of Medicine has confirmed that hypothesis. By feeding antibiotics to young mice, he has shown that the drugs drastically change the microscopic communities within their guts, and increase the amount of calories they harvest from food. The result: they became fatter.


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You are what you eat – how your diet defines you in trillions of ways


We depend on a special organ to digest the food we eat and you won’t find it in any anatomy textbook. It’s the ‘microbiome’ – a set of trillions of bacteria living inside your intestines that outnumber your own cells by ten to one. We depend on them. They wield genes that allow them to break down molecules in our food that we can’t digest ourselves. And we’re starting to realise that this secret society within our bowels has a membership roster that changes depending on what we eat.

These changes take place across both space and time. Different cultures around the world have starkly contrasting diets and their gut bacteria are different too. As we grow older, we eat increasingly diverse foods, from the milk of infancy to the complex menus of adulthood. As our palate changes, so do our gut bacteria.


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Pocket Science – when enslaved bacteria go bad, gut microbes and fat mice, and stretchy beards of iron

The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I’m really enjoying this, for quite unexpected reasons. It’s forcing me to flex writing muscles that usually don’t get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.

One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I’m keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We’ll see how that works for the foreseeable future.

Rising DAMPs – when enslaved bacteria turn our bodies against themselves

Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.

All of our cells contain small energy-supplying structures called mitochondria. They’re descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They’ve come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.

This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called “systemic inflammatory response syndrome” or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why – SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is “damage-associated molecular patterns” or DAMPs.

More from Heidi Ledford at Nature News

Reference: Nature DOI:10.1038/nature08780

Different gut bacteria lead to mice to overeat

On Wednesday, I wrote about the hidden legions residing up your bum – bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.

Vijay-Kumar’s mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin – classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.

Vijay-Kumar thinks that without the influence of TLR5, the mice don’t know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.

Read an amazing take on this from Carl Zimmer at the Loom and a previous post from me

Reference: Science DOI:10.1126/science.1179721

The stretchy iron-clad beards of mussels

For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes – mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they’re so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering – hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.

The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that’s much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other – this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten – this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.

It’s unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple – changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That’s the difference between the tighter granular bundles, and the looser ones they sit among.

More from Eric Bland at Discovery News and stories of bioengineering from me, including triple-armoured snails, shatter-proof teeth and sharp squid beaks.

Reference: Science DOI:10.1126/science.1181044

Cause of dinosaur extinction revealed confirmed

Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise – legions of zombies armed with chaingu… wait… oh. Right. An asteroid. You knew that.

More from Mark Henderson at the Times

Reference: Science DOI:10.1126/science.1177265


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Gut bacteria – fat or thin, family or friends, shared or unique

You are not alone. Even if you’re currently reading this in complete isolation, you are still far from a singular individual. You’re more of a colony – one human, together with microbes in their trillions. For every one of your own genes, your body is also host to thousands of bacterial ones. Some of the most important of these tenants – the microbiota – live in our gut. Their genes, collectively known as our microbiome, provide us with the ability to break down sources of food, like complex carbohydrates, that we would otherwise find completely indigestible.

Peter Turnbaugh from the Washington University School of Medicine has spent his career studying the microbiome. His latest work reveals both tremendous differences and similarities between the bacterial tenants of our digestive systems. Your bowels may be home to very different species of bacteria to mine, but both our sets share a core group of genes.

Turnbaugh likens the situation within our guts to that of islands. Real islands may be home to very different species of animals but all have representatives that perform certain roles; there will always be grazers, predators, insect-eating specialists, fishermen and so on.  Across islands, animals approach a set of core lifestyles in different ways, and so it is with the microbiota – every man is an island, home to unique collections of bacteria that nonetheless carry out some core functions. And the further an person’s microbiota strays from this standard template, the more likely they are to be obese.



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Human gut bacteria linked to obesity


Blogging on Peer-Reviewed ResearchThere is a widespread belief, that being overweight or obese is a question of failing willpower, fuelled in no small part by food, fitness and beauty industries. But if we look at the issue of obesity through a scientific spyglass, a very different picture emerges. Genes, for example, exert a large influence on our tendency to become obese often by influencing behaviour – a case of nature via nurture. But it’s not just our own genes that are important.

713px-escherichiacoli_niaid.jpgIn terms of processing food, humans are hardly self-sufficient. Our guts are the home of trillions of bacteria that help to break down foodstuffs that our own cells cannot cope with. Together the genes expressed by these intestinal comrades outnumber our own by thousands of times, and yet we are still largely in the dark what they do.

Over 90% of these bacteria, collectively known as the microbiota, come from just two groups – the Bacteroidetes and the Firmicutes. Now, new research suggests that the proportion of these groups is linked to the risk of becoming obese.


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Obesity amplifies across generations; can folate-rich diets stop it?

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Many measures to curb the obesity epidemic are aimed at young children. It’s a sensible strategy – we know that overweight children have a good chance of becoming overweight adults. Family homes and schools have accordingly become critical arenas where the battle against the nation’s growing waistlines is fought. But there is another equally important environment that can severely affect a person’s chances of becoming overweight, but is more often overlooked – the womb.

Overweight parents tend to raise overweight children but over the last few years, studies have confirmed that this tendency to transcend generations isn’t just the product of a shared home environment. Obesity-related genes are involved too, but even they aren’t the whole story. Research has shown that a mother’s bodyweight in the period during and just before pregnancy has a large influence on the future weight of her children.

For example, children born to mothers who have gone through drastic weight-loss surgery (where most of the stomach and intestine are bypassed) are half as likely to be obese themselves. On the other hand, mothers who put on weight between two pregnancies are more likely to have an obese second child. In this way, the obesity epidemic has the potential to trickle down through the generations, like a snowball rolling its way into an avalanche.

Now, Robert Waterland from the Baylor College of Medicine has demonstrated how the snowball gains momentum by studying three generations of mice that have a genetic tendency to overeat. And using a special diet that was high in folate and other nutrients, he found that he could stop the snowball’s descent and spare future generations of mice from a heightened risk of obesity.


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Making sense of obesity genes

Blogging on Peer-Reviewed ResearchThis is a quick follow-up to my other post on fat cells, which as it happens, isn’t the only obesity-related story out today. Another paper found a common genetic variant that increases the risk of obesity in its carriers.

A huge team of researchers scoured the genomes of almost 17,000 European people for genetic variations that are linked to obesity. Until now, only one has been found and it sits within a gene called FTO. This new study confirmed that FTO variants have the strongest association with obesity, but in the runner-up position is another variant near a gene called melanocortin-4 receptor or MC4R.


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Fat cell number is set in childhood and stays constant in adulthood

Blogging on Peer-Reviewed ResearchAs fat people have an abundance of fat tissue, the natural assumption is that fat people have more fat cells, or ‘adipocytes‘. That’s only part of the story – it turns out that overweight and obese people not only have a surplus of fat cells, they have larger ones too.

Adipocytes.jpgThe idea of these ‘fatter fat cells’ has been around since the 1970s. But their importance has been dramatically highlighted by a new study, which shows that the number of fat cells in both thin and obese people is more or less set during childhood and adolescence. During adulthood, about 8% of fat cells die every year only to be replaced by new ones. As a result, adults have a constant number of fat cells, even those who lose masses of weight. Instead, it’s changes in the volume of fat cells that causes body weight to rise and fall.

Kirsty Spalding from the Karolinska Institute in Sweden, together with a large team of international researchers, uncovered several lines of evidence to support these conclusions. Her study is a fascinating mix of cell counting, stomach surgery, radioactive Cold War fallout and a rather surprising use for carbon-dating.