'Bad' Protein Linked to Numerous Health Problems

nbahi15 writes "A report in the July 13th edition of the online Journal of Clinical Investigation has linked the aP2 protein to asthma and several other diseases. It also suggests a connection between the metabolic and immune systems and these diseases." From a related Forbes article: "To study the effects of aP2, the researchers created genetically engineered mice that could not produce the protein. 'They're metabolic supermice,' Hotamisligil said. 'We cannot make them obese, diabetic or atherosclerotic. They don't develop fatty liver disease, and they don't develop asthma.' In mice with an animal model of asthma, the researchers found that aP2 regulated the infiltration of inflammatory molecules into the lungs."

Comments

Bad aP2Ps.

[m_chan]

Great. Kazaa just gave me asthma. Well, let's just get the MPAA and the RIAA to file some lawsuits against these bad aP2Ps. That'll fix their wagon. They've got to learn that it's wrong to steal the pharmaceutical industry's property. Wait. What?

My Question

[MyLongNickName]

If these proteins are so bad, and so easy to genetically engineer out, then from an evolutionary standpoint, why do we have these genes? Are we sure this protein doesn't have a big positive effect that we are not aware of?

Re:My Question

[Anonymous Coward]

Are we sure this protein doesn't have a big positive effect that we are not aware of?

Yes. This is the gene that prevents you from turning into a super mouse. For everyone except mice, that's a major positive effect.

Re:My Question

[Mprx]

The protein is associated with diseases that mostly happen in later life, so there will be very little evolutionary pressure to remove it. Evolution optimizes for reproductive fitness only, and as elderly mice do not look after their young, genes that improve survival in old age will not be selected. It would require only a minor benefit in youth to evolve a gene which causes harm in old age.

Re:My Question

[darkmeridian]

To get evolved out, a gene would have to kill the carrier before reproduction age. Men used to live short lives, and the diseases prevented by the genes weren't weeding cavemen out as much as the sabretooth tigers and infections were. Furthermore, the diseases caused by the genes, such as diabetes, heart attacks and asthma, probably were not a huge problem in a pre-industrial society that did not have excess carbohydrates, processed sugars, and artificial pollutants. Evolution isn't a process where a divine being aspires towards perfection. It is trial and error. If there is no selective force, then imperfection remains. That's what is happening here.

Re:My Question

[imsabbel]

Because in a real enviroment, you actually WANT to get fat in times you have more than enough food.
You know, the whole fat==energy storage thingy.

Re:My Question

[Vellmont]

If these proteins are so bad, and so easy to genetically engineer out, then from an evolutionary standpoint, why do we have these genes?

The gene is linked to obesity, heart disease, diabetes, and asthma. Obesity has only become a problem within the last hundred years or so as we've become more sedentary and gotten access to more food. Heart disease has increased because of a recent increase in saturated and trans-fats in our diet. Also, heart disease tends to kill people after they've raised children, so after you've passed on your genes. The article doesn't specify which type of diabetes this protein is linked to, but type II diabetes is linked with obesity (see obesity), and simply old age (already raised kids). Asthma is mostly caused by pollution, and possibly an overly hygenic environment during childhood (though there's genetic risk factors of course) which are both recent phenomenon.

The point is that it could easily be that this protein hasn't posed a threat to us until very recently when our lifestyle has changed drastically. The gene that produces this protein wouldn't be eliminated if in the past it posed no threat to producing offspring and raising them to maturity.

Re:My Question

[MyLongNickName]

None of those sources indicate a 90% decrease. One says 25-50%.

Another babbles "WE should try to make our mind like land, because land has beautiful virtues, when animal put their excrement on land, it (Land) never express anything angrily, because it (Land) is not swayed or completely indifferent, when human (rich, famous, sage, saint, or perfect people) walk over land, it (Land) feels nothing too, again because it (Land) is not swayed or completely indifferent."

And this is one of the more coherent passages.

I will now erase any memory of this coversation from my memory to make room for something useful.

Re:My Question

[mnmn]

You're right.

Supermetabolic mice will sound nice in the 21st century when everyone is trying to lose weight, and anyone going hungry isn't connected to the Internet. It sounds like 'too much metabolism', which would be terrible during the ice age when people went hungry and wanted to conserve energy.

Genetically engineer yourself without a2P and end up on a deserted island; you'll be the first to die. In many ways its similar to stapling your stomach, you'll need constantly more food. However you might also be hyperactive, incapable of sports like playing golf, precision work that requires patience etc.

Ideally there'd be a pill that would counter a2P for everyone who wants it, so theres no permanent change. It should be a hit like Viagra.

Re:My Question

[krmt]

The Drosophila version of this protein has been shown to be absolutely required for creating leg joints. Without it, you get flies with short stubby legs that can't walk, and as a result die. See this paper for details.

The knockout mice mentioned above also have major problems, from a brief search of the literature. See this and this for example. This implies that the protein has critical functions that are so important that they are somewhat conserved all the way from flies to humans. So important, it seems, that the negative effects of having the protein don't outweigh the positive ones.

Re:My Question

[Anonymous Coward]

Actually, that particular conjecture in the study is piss poor if you look at it closely. The conjecture is based on a survey conducted on members of Mensa. Mensa is nowhere near a good representative cross-section of smart people. It boggles the mind, really, how the authors made the leap from the fact that Mensa has a higher percentage of asthmatics and myopes than the average to a correlation between asthma and myopia and intelligence. That is grossly inaccurate.

The only conclusion that you can draw from their study, with respect to this particular topic (which, incidentally, is just a small sidenote in the study), is that there is a correlation between asthma and myopia and Mensa. That's a no-brainer, really. Mensa is self-selected for people whose primary interests are purely intellectual. Myopes and asthmatics are physically predisposed towards activies like those conducted by Mensa. Duh. They seem to have forgotten that there are many people, such as myself, who've posted scores that would allow them into Mensa, but decline to join because their interests lie in areas other than brainteasers and discussions.

You cannot draw statistically valid conclusions about an entire population by studying a self-selected subset of that population.

Re:My Question

[SlickCow]

Remember, correlation vs causation. I can see it as being likely that people who are vegetarian for over 20 years are also health nuts in many more useful ways (exercise, for example). Therefore, there is reason to believe the correlation between healthfulness and vegetarianism doesn't necessarily come from not eating flesh, but from other aspects of their life.

Re:My Question

[ocelotbob]

Could it actually be a secondary side effect? That because someone is asthmatic, they're more likely to engage in more mentally stimulating activities, due to the fact that physical stimulation is off limits?

Re:My Question

[Maxo-Texas]

Something not considered in most of these studies is:

Is RED meat bad for you or..

Is RED meat raised on pesticide polluted corn instead of grass, shot full with hormones and drugs bad for you.

Is CHICKEN bad for you...

Is CHICKEN raised in pens with thousands of others in a highly stressful, low exercise, drug/hormone/pesticide polluted environment bad for you.

I personally think that a lot of the benefits of vegetables, beef, and chicken are not present in factory raised conditions. You have a tomato that *looks* like a tomatoe but which is 80% fiber (so it ships well) and lacks the nutrients. Chicken and beef are good because they eat tons of bugs and plants and concentrate the nutrients and minerals in those plants and we adapted to eating those kinds of animal meats. We have not yet adapted to eating meat that looks like meat but which has different nutritional value than it used to.

Re:My Question

[Joebert]

Genetically engineer yourself without a2P and end up on a deserted island; you'll be the first to die

As an ironic side effect, you just might also be the last.

Re:My Question

[mlush]

"A vegetarian lifestyle of long duration (> or = 20 y) "

Vegetarians don't live longer it just seems longer

Re:My Question

[Artifakt]

Overall, you make a good arguement, except on one point where you put it one way in your first paragraph, and the other in the last sentence. Your second version is right, where you inculd raising and not just bearing the offspring.
        For mammals, there is selection pressure well after offspring are produced. For humans in particular, far more children tend to survice until they themselves can reproduce if those children have good parenting. Alternately, this can be expressed as: People who die before they get their children raised to self sufficiency represent a bad trait that natural selection theoretically should put some pressure against. This probably is the explanaiton why humans are unusual among mammals in that they often live well past menopause ages, as even grand-parents or great grand-parents may be able to increase the survivability of subsequent generations.
        However, there are some alternatives that help soften the selection process. A lot of human social institutions are developed to shift this load from biological parents to the rest of the species: Orphanages (obviously), but also schools, adoption/fosterage, and in some cultures, even military service (i.e. 11 year old tribal soldiers in places like Somalia or Riwanda). Probably even prehistoric humans had some of these institutions - for example there are Neandertal examples that show some seriously geriatric types, with advanced arthritis, osteoporosis, and injuries sustained 30 or more years before death, who were still kept alive by the rest of the tribe. Humans have been finding some advantages in what would seem at first glance a disadvantagous situation for apparently upwards of 100,000 years.
        Unfortunately, Even though all these conditions such as heart disease do greatly impact survival, they aren't common without abundant food. Nature hasn't had many generations to select against them. The gene primarily involved wouldn't be eliminated even if it did pose a threat chiefly to just the raising to maturity part, as that threat was largely masked by other genes that were under more pressure at the time, because they threatened even initial reproduction.

Re:Prions?

[john83]

Wow. Someone among the first ten posts didn't post an "I for one ... mouse overlords" cliche.

No, it seems to me that these proteins are made by the body, while prions are infectious agents (though made entirely of protein themselves).

Re:Someone's got to say it

[Conception]

No, really... no one has to say it. I promise. It can not be said. We'll all be fine.

Re:Someone's got to say it

[Red Samurai]

Sorry, apparently this was branded "not funny" a while back by the joke police.

Original quote included side-effects

[MarkByers]

would be nice if they listed some side effects

See the original quote in full:

All the mice died instantly, but on the positive side we cannot make them obese, diabetic or atherosclerotic. They don't develop fatty liver disease, and they don't develop asthma.

Apparently dead mice don't have much appetite. The scientists are continuing their investigations.

no useful function?

[m874t232]

Called aP2, the protein has no useful function in the body. It only appears during the course of disease, and seems to cause adverse effects on blood sugar levels and fatty acid metabolism.

Proteins without useful functions tend not to stay around in populations. Chances are that this protein is important for something. Good candidates are fighting off various parasitic infections, or dealing with some kind of physiological stresses. Those conditions may not arise much in Western lifestyles, and hence getting rid of aP2 may be a good idea for us, but the protein almost certainly has some kind of useful function under some conditions.

Re:no useful function?

[Mr. Flibble]

Proteins without useful functions tend not to stay around in populations. Chances are that this protein is important for something. Good candidates are fighting off various parasitic infections, or dealing with some kind of physiological stresses. Those conditions may not arise much in Western lifestyles, and hence getting rid of aP2 may be a good idea for us, but the protein almost certainly has some kind of useful function under some conditions.

Or, it is like the appendix, or some othe holdover. It could be something that once was useful somewhere in other species, and is now not harmful to a individual until later in life, after reproduction years are passed. However, I agree with you, it most likely performs some function that is now likely obselete in our lifestyle, however, I always try to spin more than one hypothesis on any given idea. (The question is, do all species in kindom Mamimalia have this protien?)

Re:no useful function?

[E 99]

Or, it is like the appendix, or some othe holdover.

Furthermore, it's not clear that the human appendix is entirely without function; it may contribute to immune system function, at least early in life.

Actually, today the appendix is well-understood to be a fully functional organ of the immune system. It tells lymphocytes where to go to fight infections, and it boosts the large intestine's immunity to various foods and drugs. (But it should still be recognized that our current ignorance of the workings of the immune system makes our current knowledge of it look like a joke.)

Re:no useful function?

[kozumik]

Proteins without useful functions tend not to stay around in populations. Chances are that this protein is important for something.

If the protein is created by the combination of an ordinarily inert gene and modern environmental conditions (i.e. obesity in the modern calorie abundant and sedentary environment) then the protein would not historically have been "around in populations" and the gene would not have been selected out.

You're making a common mistake, assuming that because nature has evolved us to be fairly optimal/healthy for past historical conditions, that we're optimized by evolution in a general sense for all time; or that all we're evolved to desire is good in the present. Not so.

We're optimized for a very different world then we've created, and in many ways we're maladapted to modern living. Evolution never planned for us getting everything we want or the option to sit all the time and eat as much as we like. In fact our desires are evolved to be healthy in accordance with the scarcity principle i.e. we desire most strongly that which is both needed and scarce.

Things which are historically needed but plentiful are often taken for granted and we've evolved mechanisms to effortlessly prevent gorging on them. Take breathing oxygen for example. Gorging oneself on oxygen isn't exactly a deadly sin because its levels have been plentiful throughout evolutionary history hence we evolved to take just as much as we need. But gorging on eating was recognized as "sinful" when it became possible with the advent of agriculture and when it became necessary for culture to address the inadequacy of evolved instinct to present conditions. We've been dealing with obesity and the "sin" of gluttony ever since.

aP2 Proteins

[thorshammer42]

So that's that secret ingredient in my Big Mac!

Humans arent fit for breeding.

[elucido]

IF we follow your logic to it's conclusion, the human species is unfit for breeding. Let's see, every human dies, and will die at an earlier and earlier age as pollution decreases lifespan. So according to your own logic, you adocate suicide?!

In nature, the fit are the ones who declare themselves fit. If obese out of shape old men declare themselves more fit than young teenagers in their prime, then they are more fit. Do you see that animals actually have brains and decide among themselves who will be fit and when? Second animals are not rational, mice will decide their individual families are fit even if they arent. A family of fat mice working together might be more fit than a group of independent skinny mice. Lastly, fitness of the individual mouse has nothing to do with fitness of the individual species.

So, we could pick out the most beautiful atheletes, but if they have the smallest brains, well, thats going to limit the overall long term survival of the species.

Logical flaw in your arguement :"Everyone wants to look good, but do you want the species to look good, and be incredibly lazy, eventually to the point of not even bothering to breed anymore."

This is an assumption, and what is the basis? If you view yourself as a physical body, and not a part of an ecosystem, then yes how your body looks matters, but obesity really has nothing to do with fitness as in the right environment being obese will keep you from starving and is physically attractive. The way to survive is intelligent selection, and most humans don't intelligently select. Natural selection isnt always intelligent. Intelligent selection is selecting the human most likely to improve the quality of the species itself, which almost no one does. Geeks get no love, and geniuses often get treated like somethings wrong with them. If the goal is the survival of the human species on a long term basis, it's intelligent selection. If the goal is survival of the fittest by todays standards, at the cost of tomorrow, well then mate with the most physically attractive person you can find, and in the future you will have a physically attractive yet most likely extinct human species. What you have to understand is, the long term survival of a species requires both the obese genes and the skinny genes, it requires both the lazy and hard working, it's the lazy who created the personal computer and increased productivity, otherwise we'd still be using typewriters. It's the lazy who invented the car, the bike and modern transportation. It's the lazy who invented the factory.

It could be that we are far too lazy, I will not say too much lazy is good, but there is a need for lazy. There is a need for hard labor. Most importantly, we have a shortage of intelligent minds, and a massive over supply of simple minds. Many people, are happy to just party through life, and expect life to get better, and then be surprised as each year progressively gets worse. If you want the key to survival of the fittest, mate with the people who make your life and other peoples lives better, you can be sure the offspring will carry that gene, otherwise you'll mate potentially with a person who will make your life and everyone around you miserable, and we already know where this can lead, a divorce perhaps? But it has a much greater impact on the lifespan of yourself as an individual, and on the lifespan of the species itself than people realize.

natural way to lower ap2

[osho_gg]

If you read the forbes article it mentions that a natural way to reduce the "bad" ap2 protein is to lose weight if you are over-weight and maintain a healthy weight. It is amazing how so many illnesses can be avoided by just staying in shape and regularly exercising.

And, this way is a lot safer that subjecting your body to pre-clinical drugs tried only on mice.

Osho

Re:natural way to lower ap2

[Anonymous Coward]

Reversing weight gain is like reversing gray hair. You will lose, and you will make yourself miserable in the process. Unless you happen to be one of the lucky 5% of the people who have a genetic predisposition that allows you to keep it off relatively easily.

WTF? Where are you getting your information? What's with your defeatest attitutde? What, we're just all supposed to accept the fact that we're all going to become obese (except that "lucky 5%"?).

Seriously, obesity in America much, much worse than 20 years ago. The CDC has been tracking the rise of adult obesity, and it's pretty shocking. Fast food, junk food, huge portions have been around for 20 years, it's not like American bodies all suddenly developed glandular problems. It's our lifestyles that have changed, and it's not impossible to change it back.

Re:natural way to lower ap2

[ShakaUVM]

You can lose weight, it just isn't easy.

I've been doing martial arts for 10 years and seen lots of people lose weight on it. Walking isn't really high intensity enough.

Don't draw conclusions

[Pedrito]

It's far too soon to draw any conclusions about this. Yes, removing it appears to have a positive effect on mice. Mice, as some people have to be reminded, are not people. Others have mentioned this protein may have a positive effect. It may. It may have a crucial effect in people. We've cured just about every type of known cancer in mice in about a few dozen different ways and yet the cures for these cancers in people continue to elude us.

Now that said, it doesn't mean that more research isn't in order. At some point, they'll want to create a drug that binds to or otherwise inhibits this protein and then probably test it on primates. Who knows, it may turn out to be a wonder cure for asthma and obesity and other things. But it's FAR too soon to draw that conclusion. There's a lot of amazing research going on out there, but this is simply one of many pieces of research that come up witht these kinds of positive results every week. Most don't pan out and until they have a drug for people, it's hardly worth mentioning on Slashdot. If Slashdot mentioned every one of these, that'd be all it did.

The problem with this talk of evolution

[elucido]

People talk about evolution as if we do not control it. Evolution has been a controlled art for a while now, and obviously we are getting it wrong because, well look around you. Sure we could focus on improving our species and our evolution, but it has nothing to do with natural selection, thats ignoring the fact that we have science and brains capable of actually directing our own evolution. Our lack of evolution is due to the fact that we just recently discovered genetics, and even now while we know what genetics is, we rely on religion to tell us how to evolve and live. We are focused a bit too much on appearance and not really focused at all on survival. Read up on transhumanism.

Re:Vegetarians are not healthier

[arose]

A genetically engineered veggie is no healthier or safer than eating the steak [..]

Has all genetically modified food been shown unhealthy or something? Or may it be that you have turned of your brain with irrational fear? What we have actualy have to look out for are dangerous things poduced as a side effect of specific genetic modifications, not some imagined nastienes found in all modified food.

aP2, not a2p

[smcdow]

Instead of aP2, I read a2p, which is the awk to perl translator. Everybody knows a2p is bad for you. First I've heard of aP2.

Re:Prions?

[zip0nada]

Not Really, Prions are foreign proteins than convert regular proteins into identical molecules. aP2 on the other hand is a protein produced by the body that simply makes things worse. Of course, this is over simplifying a bit but you can read the article and the wikipedea article http://en.wikipedia.org/wiki/Prion and see for yourself.

Re:Six thousand years

[vidarh]

If humans have undergone mutations at such a high rate that we could've ended up as we are from a "good" design in 6000 years, then that itself would be an argument against intelligent design - it would mean the odds of intelligent life spontaneously arising would need to be far better than even the most optimistic supporter of evolution would dream of suggesting.

what about catyclismic events?

[plasmacutter]

It may be bad for us now.. but it apparently helps us more efficiently process foods and store energy (that is what fats are, stored energy).

Sure we have an abundance of food and a sedentary lifestyle now, but our society is quite fragile. If some catyclism were to happen, such as the mile high pacific tsunami predicted if that shelf of hawaii (which is sliding) were to suddenly give way, then we may lose that infrastructure.

If we engineer out or impede this gene, we may end up going extinct in the absence of abundant food supplies, which exist now only because we are artifically, and some argue only temporarily, increasing the carrying capacity of our planet.

Wrong Protein

[Ken_g6]

I did a Google search on "aP2", and I noticed two distinct types of results. It looks like "aP2", which the main article discusses, and "AP-2", which is discussed in the articles you linked to, are two very different proteins, with confusingly similar abbreviations.

"aP2", the topic of the main article, is the "adipocyte lipid-binding protein", also known as "ALBP".

"AP2", or "AP-2", is "Activator protein 2" or "Activator protein-2alpha". It seems to be associated, not with fat, but with cancer.

Stupid

[smenor]

Stuff like this Forbes article is the reason I hate the popular press's presentation of research - especially when those doing the research are interested in self-aggrandizing (for fun or profit).

Yeah - deleting it prevents them from becoming diabetic and from developing asthma - because without it endoytosis doesn't work right, the immune response is hampered and and so some autoimmune diseases don't happen.

Deleting it also screws with absorption of lipids, hence no fatty liver disease, atherosclerosis or obesity.

In addition, it's involved in recycling of presynapric vesicle membranes so it wouldn't surprise me if deleting / blocking it had cognitive / behavioral effects.

So, yeah, it sounds like getting rid of it is a miracle cure, but (as others have pointed out), it's there for a reason.

Come on, does anyone really believe that knocking out a single protein would make a 'metabolic super-mouse'?