'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

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

[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

[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

[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

[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.

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?)

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.

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.