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'Bad' Protein Linked to Numerous Health Problems 217

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."
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'Bad' Protein Linked to Numerous Health Problems

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  • Bad aP2Ps. (Score:4, Funny)

    by m_chan ( 95943 ) * on Saturday July 15, 2006 @02:37PM (#15725236) Homepage
    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?
  • Are these "bad proteins" anything like the prions that cause mad-cow or Crutzfeld-Jacob disease?
    • Re:Prions? (Score:2, Informative)

      by john83 ( 923470 )
      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).
    • That is an interesting direction of thought. If they are, well we might already have Crutzfeld-Jacob disease. Think of it this way, if we do have it, you cannot tell anyone for the same reason you cannot talk about alien invasions and other weird unlikely events. Sure it's possible, but if we think about every possible unlikely event, we all will go batshit crazy and be wearing tin-foil hats. I don't really think tin-foil hats do much except fry your brain.

    • Re:Prions? (Score:2, Informative)

      by zip0nada ( 883919 )
      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 [wikipedia.org] and see for yourself.
  • My Question (Score:5, Insightful)

    by MyLongNickName ( 822545 ) on Saturday July 15, 2006 @02:46PM (#15725274) Journal
    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?
    • by Anonymous Coward on Saturday July 15, 2006 @02:56PM (#15725312)
      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.
    • It could have been a mutation linked to some other trait by coincidence. If the negative effect of the protein is not bad enough to kill itself off, then it will stick around.
    • Re:My Question (Score:5, Insightful)

      by Mprx ( 82435 ) on Saturday July 15, 2006 @03:06PM (#15725345)
      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.
      • I don't think a protien is responsible for aging. Look, people have been obese since the beginning and werent dying from cancer at these rates. Heart attacks were never this popular, we had kings who lived for 60+ years and they didnt die of heart attacks, simply of old age.

        I don't think just because someone dies of a heart attack, or of cancer, that we can automatically assume they would have died that way 100 years ago. The food is not the same, read the ingredients. The water is not the same either, or t
        • lived for 60+ years and they didnt die of heart attacks, simply of old age.

          Old age? Do they put that on death certificates?

          If you have a primitave understanding of medicine, and your king drops dead at the ripe old age of 60, what else are you going to say? They most certainly died of something, everyone does, it just gets more likely with every passing year.
        • The food is not the same, read the ingredients

          You're right! By god, where's the mold? Where's the rot? I can't believe i just ate meat and bread without life-sustaining rot!

          Yes, there are a lot of things in the food we eat that are new. However, at least in America, everything sold as food has to go through a more rigid inspection system than ever happened in ancient times.
          • In ancient times you hunted and grew the food yourself. Why would you need to have some complete strangers who don't know you inspecting your food? In ancient times you were personally responsible for your own food because there was no super market.

            I honestly think, that if you allow your food to go rotten then you should have salted it first and dried it. You act like ancient people were stupid or something, but it does not take a rocket scientist to figure out how long food will keep before going bad, or
        • I don't think a protien is responsible for aging.

          You DO know what causes aging in humans, right? The shortening of telomeres on our chromosomes, caused by errors in copying.. you got it.. proteins. You DO know what causes those errors, right? You got it... more proteins (and some free radicals and other toxins here and there, toxins which are becoming increasingly common I might add).

          Look, people have been obese since the beginning

          No, no they haven't. Obesity for our ancestors meant death, because a

          • So many assumptions. First there are MANY theories of aging. Some say it's genetic, some say aging has to do with how many calories you consume, and some say aging has to do with many other factors, but lets assume it's free radicals. Eventually the air and water will age you twice as fast as it does now.

            Let's also say, that you are wrong, heart attacks did not exist in the past, so while you are right being obese meant you werent as good of a hunter, you don't have to be a hunter because you are obese. so
      • Evolution optimizes for reproductive fitness only

        No offense meant, but that (and the assumption that evolution is only relevant to reproductive age made by another poster) is actually false and a rather unfortunately common over-simplification of evolution. It presumes every gene must manifest in every individual during reproductive age and lead directly to reproduction to be of value. Not so.

        Darwin and serious evolutionary biologists since have understood that's false; and in fact fails to explain the evol

        • You're assuming too narrow a definition of "reproductive fitness". It means not only having children, but those children having children of their own, and also relatives having many descendants. This certainly can allow for evolutionary pressure past reproductive age, but in mice this is minimal.
    • Re:My Question (Score:5, Insightful)

      by darkmeridian ( 119044 ) <william DOT chuang AT gmail DOT com> on Saturday July 15, 2006 @03:06PM (#15725347) Homepage
      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.
      • Asthma, as I can attest, is definitely not a competitive advantage. My 10,000x great grandpa with asthema tries to outrun a saber tooth tiger, but can't get enough air to keep up pace. My ancestors suddenly do not exist.

        On an interesting note, allergies and asthema are related to high IQ. Coincidence?
        • Care to cite a source for that? As someone with both allergies and a high IQ, that still sounds like something that the scrawny kids tell themselves to feel better when they can't keep up in gym class.
          • Re:My Question (Score:2, Interesting)

            Here is an excellent one: link [soton.ac.uk].

            One exerpt: 21. Like myopia, the higher one's intelligence, the more likely one is to be allergic to inhaled substances and, thus, to have asthma. For example, in the study of 2,720 gifted people conducted by this author, more than 80% of those who reported having asthma also had allergies; here, the gifted females were also far more likely than the males to have these disorders, and myopes were nearly twice as likely as non- myopes to have severe or multiple allergies (see se
            • Re:My Question (Score:5, Interesting)

              by Anonymous Coward on Saturday July 15, 2006 @04:44PM (#15725639)
              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 (Score:4, Interesting)

              by ocelotbob ( 173602 ) <`gro.bobtoleco' `ta' `toleco'> on Saturday July 15, 2006 @05:03PM (#15725699) Homepage
              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 (Score:3, Interesting)

        by mnmn ( 145599 )
        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
        • Re:My Question (Score:2, Insightful)

          by Joebert ( 946227 )
          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.
      • 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
        • That people die from heart disease, obesity, and diabetes seems like proof positive that selective force is being applied. That coupled with children being born later, and people choosing not to have children, also select towards healthier, stronger, and more fertile people.

          If we can continue selecting for later childbirth and healthier parents for the next hundred years, we may see some real evolution at work.
          • I don't understand your logic. What does death have to do with health if everyone is sick? you seem to think there will be mutants on earth who won't die and who will have lots of kids but the trend is that we all are dying sooner and having less kids, with no real genetic exceptions to this rule. So sure there are selective forces, but it is unclear if anyone gains from them. And why are you confident humans will even exist in 100 years?
      • If you have a population of creatures that share an ecological niche, and one has this mutation that allows them to be more successful and thus drive the non-mutated population toward extinction, then the mutation becomes self-selecting and becomes predominant.

        It is not strictly necessary that the mutation acts before reproduction.
    • Re:My Question (Score:3, Interesting)

      by imsabbel ( 611519 )
      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 (Score:5, Informative)

      by Vellmont ( 569020 ) on Saturday July 15, 2006 @03:16PM (#15725377) Homepage

      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 (Score:5, Insightful)

        by Artifakt ( 700173 ) on Saturday July 15, 2006 @06:30PM (#15725944)
        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.
        • 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.

          Quite a valid point, but from an evolutionary basis, surviving till you're 25-30 (two quick generations) is far easier than surviving till you're 40-50, which is where obesity and heart disease really get nasty.

      • by plasmacutter ( 901737 ) on Saturday July 15, 2006 @07:44PM (#15726133)
        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.
      • "Obesity has only become a problem within the last hundred years or so"

        "Heart disease has increased because of a recent increase in saturated and trans-fats in our diet."

        "Asthma is mostly caused by pollution"


        None of these are true. The cultivation of grains and starchy tubers is what caused it. Morbid obesity, most often seen in the US, is a result of overyly processed foods of the wrong type.

    • because up till recently this hasnt been detrimental? Having a metablosim tha hoarded fat was a good thing, because you never knew where your next meal was coming from. IM not sure. But there are lots of things that are harmful today that were benefical in the past. Look at cicle cell disease, it dosent make sense unless youre living in africa.
    • Perhaps being "so bad" is not so bad from an evolutionary standpoint -- after one has passed the age where one can pass on one's genome, it's considered a success from the point of view of the genome. Maybe removing the organism that competes with its offspring for resources is considered beneficial from a genome's perspective.

      Another possibility is that these proteins may be produced by any of several common mutations of the genome, so that it will spontaneously reoccur in organisms that have managed to l
    • If these proteins are so bad, and so easy to genetically engineer out, then from an evolutionary standpoint, why do we have these genes?

      Because evolution takes a loooooong time to make changes. You're still born with an appendix, after all, even though it serves no useful function for modern humans.
    • Re:My Question (Score:5, Interesting)

      by krmt ( 91422 ) <(therefrmhere) (at) (yahoo.com)> on Saturday July 15, 2006 @04:40PM (#15725631) Homepage
      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 [nih.gov] for details.

      The knockout mice mentioned above also have major problems, from a brief search of the literature. See this [nih.gov] and this [nih.gov] 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.
      • Wrong Protein (Score:4, Informative)

        by Ken_g6 ( 775014 ) on Sunday July 16, 2006 @12:30AM (#15726855) Homepage
        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" [google.com] or "Activator protein-2alpha". It seems to be associated, not with fat, but with cancer.
    • If these proteins are so bad, and so easy to genetically engineer out, then from an evolutionary standpoint, why do we have these genes?
      Might be a simple case of "not bad enough".
    • 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?

      Imho that question is premised on flawed assumptions:

      1) evolution might have selected against this gene as easily as geneticists
      2) evolution had cause to, in historical context
      3) therefore the gene must have some other benefit

      The article suggests that a2P production is amplified by excessi

  • Wow, I could so go for a pill that would inhibit production of this protein as a wieght loss drug that does not rely on stimulants.
  • and it causes The Evil Bit [faqs.org], too!
  • no useful function? (Score:5, Interesting)

    by m874t232 ( 973431 ) on Saturday July 15, 2006 @03:40PM (#15725465)
    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.
    • by Mr. Flibble ( 12943 ) on Saturday July 15, 2006 @04:01PM (#15725513) Homepage
      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?)
      • Or, it is like the appendix, or some othe holdover.

        That's possible, but seems less likely. Getting rid of the appendix in evolution is difficult, since it probably requires changing the coordinated activity of many genes. Getting rid of a single protein is simple: you get rid of the gene or just alter it slightly.

        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. (And, of course, it has a major function, i
        • by E++99 ( 880734 )

          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

    • by kozumik ( 946298 )

      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

  • So that's that secret ingredient in my Big Mac!
  • by osho_gg ( 652984 ) on Saturday July 15, 2006 @04:06PM (#15725524)
    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

  • by Pedrito ( 94783 ) on Saturday July 15, 2006 @04:20PM (#15725573)
    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.
  • by smcdow ( 114828 ) on Saturday July 15, 2006 @05:02PM (#15725692) Homepage
    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.
  • well i guess some of the genes that we have programs ourselves to die. just imaging if nobody would die today. i'll just image chaos in the world due to scarce resources. going to the lemmings path?
  • I've had many girls tell me that protien makes their eyes sting. It can't be good for 'em. This is news? ;-)
  • Stupid (Score:3, Insightful)

    by smenor ( 905244 ) on Sunday July 16, 2006 @03:52AM (#15727208) Homepage
    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'?

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