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Exercise and Caffeine May Activate Metabolic Genes

ananyo writes "A trip to the gym could mean not just losing pounds — but also chemical modifications from DNA in the form of methyl groups. The presence (or absence) of methyl groups at certain positions on DNA can affect gene expression. Researchers at the Karolinska Institute in Stockholm looked at the methylation status of genes in small biopsies taken from the thigh muscles of healthy young adults before and after a stint on an exercise bike. They found that, for some genes involved in energy metabolism, the workout demethylated the promoter regions (stretches of DNA that facilitate the transcription of particular genes). Genes unrelated to metabolism remained methylated. Furthermore, similar demethylation could be seen when cultured muscle cells were given a massive (probably lethal) dose of caffeine."

25 of 148 comments (clear)

  1. Exercising easier? Really? by alesplin · · Score: 4, Funny

    From TFA: ...“one would need to consume a caffeine equivalent of about 50 cups per day, almost close to a lethal dose”, she says. “Exercising is far easier if you ask me.” Clearly, she doesn't know about the secret Mountain Dew IV that hackers use whilst lurking in their parents' basements...

    1. Re:Exercising easier? Really? by MrEricSir · · Score: 3, Funny

      Right, because nobody ever gets fat from Mountain Dew.

      --
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    2. Re:Exercising easier? Really? by babblefrog · · Score: 4, Informative

      A 20 oz Mountain Dew contains approximately 19 tsp of sugar. Calibrate accordingly.

    3. Re:Exercising easier? Really? by marnues · · Score: 3, Interesting

      You certainly know how to spit out studies, but you seem to have missed a lot of connection.
      First off, sugar's affect on metabolism is not linear. Ingesting a little sugar may increase the body's caloric need above the sugar's caloric content. Ingesting a lot of sugar definitely does not. Otherwise a mountain dew would be some unbelievable drug with lethal consequences.
      Secondly, sugar comes in many forms, and those forms are packaged in various substances. No substances will have exactly the same affect on the body as another. Getting to the sugar in a sugar pill may be the cause of the increased caloric need while getting to the sugar in a mountain dew requires almost no change in caloric need.
      Thirdly, bodies digest substances differently based on state. If I've been to the gym for an hour everyday for a year, my body won't notice much difference between the sugar pill and nothing at all. If my metabolic rate is effectively zero though, the sugar pill can have notice effects, as any ingested substance can.

    4. Re:Exercising easier? Really? by Auroch · · Score: 3, Informative

      If your goal is "weight loss" then eating less is far easier and more effective than trying to burn it off at the gym. Going to the gym often makes you eat more when you get home - making it a waste of time.

      (Yeah, I know it's heresy in the USA to say gym isn't the answer to everything...)

      ... Wrong. Eating less will only work for a while, and only if it is a moderate decrease. You burn most of your calories due to metabolic rates, and the best way to increase your metabolism is to build muscle. So no, you don't have to go to the gym. And cardio won't really do it for you either. But you do need to bulk up on your muscle mass.

      Example - an hour of cardio will let you burn about 300-400 calories. Increasing your base metabolic rate by 10% will let you burn the exact same amount with absolutely NO cardio. So if you drop about 5-10% of your body fat and turn that into muscle, you'll lose the equivalent of an hour of cardio (a DAY), simply by going to the gym 3x a week and doing weights. It'll probably take you about 2 months @ 3x half an hour (so 1.5 hours a week over 8 weeks) a week to see that muscle increase, but you'll be getting the equivalent of a 7 hours a week of cardio for weight loss.

      Or you could continue to believe whatever pseudoscience you're spouting (and probably read in "mens health" or equivalent trash magazine) and stay fat.

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  2. Let's stop exercising? by Anonymous Coward · · Score: 3, Funny

    FTFA:

    Zierath cautions that this result does not imply that drinking coffee could be a replacement for exercise. Caffeine acts mainly through the central nervous system, and to see direct effects on muscle such as those in the rodent-cell experiments, “one would need to consume a caffeine equivalent of about 50 cups per day, almost close to a lethal dose”, she says. “Exercising is far easier if you ask me.”

    It's hard to code while I exercise, and it's only almost close a lethal dose. If it doesn't kill me, will 50 cups of coffee make me stronger? ;)

    1. Re:Let's stop exercising? by dr2chase · · Score: 4, Funny

      It'll make you stranger, more likely.

  3. Translation? by slasho81 · · Score: 5, Insightful

    Can we get an English translation of the summary?

    1. Re:Translation? by Deathnerd · · Score: 4, Funny

      Agreed. I can't make heads or tails whether having my DNA promoter regions methylated or demethylated is good for me or not.

    2. Re:Translation? by biodata · · Score: 5, Informative

      I think it may be the other way round, if I have it right - methylation of the promoter region stops the gene being activated. The promoter is the DNA 'upstream' of the gene, usually, where the trasnscription machinery binds to begin reading off the gene and producing messenger RNA. If the promoter is methylated, the DNA doesn't unwind to provide access to the machinery. The researchers found that 'useful' metabolic genes were demethylated (so activated) by exercise and caffeine.

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    3. Re:Translation? by Anonymous Coward · · Score: 3, Informative

      Being methylated activates the gene. It depends on the context if it is good or bad. For example, a growth gene might be good during development, but might be bad in the case of cancer.

      IAAB, and you have this backwards. Methylation is associated with gene silencing, and demethylation with activation. The extra methyl groups may in many cases inhibit the binding of transcription factors, which tend to favor canonical, unmodified DNA. This is also mentioned in TFA.

      Of course, in biology, nothing is certain, and I'd bet that someone's found a transcription factor somewhere that binds to methylated DNA and preferentially activates genes in methylated regions, but the general trend is that demethylation promotes activation.

    4. Re:Translation? by rgbrenner · · Score: 5, Funny

      slashdot... where two posts saying exactly the opposite of each other are both marked +5 informative.

    5. Re:Translation? by Crypto+Gnome · · Score: 3, Funny

      Excellent!
      I've been looking for Miss Wright for quite some time!

      --
      Visit CryptoGnome in his home.
    6. Re:Translation? by Randle_Revar · · Score: 5, Informative

      Correct, methylation stops gene expression. Mod Parent up, grandparent down

      http://www.sciencedaily.com/releases/2007/04/070421211622.htm

    7. Re:Translation? by Samantha+Wright · · Score: 3, Interesting

      As requested, I put a car-related analogy here. Since you technically asked a slightly different question, though, I'll give you a computer analogy to round things out.

      Imagine you had an incredibly weird job scheduler that evaluated a huge probabilistic boolean expression, and then ran a given program afterwards if the expression evaluated to true. Then imagine that it ran this check several million times per second, and that all of the programs currently running had access to all of the variables used by all of the conditions, and could change them at any time. This is, essentially, how the cell decides what genes to express normally. No gene is ever expressed with 0% probability or 100% efficiency.

      Methylation is like commenting out individual lines of code. An effect similar to block comments—with the same hilarious consequences if you make a typo in the end tag—is produced by another mechanism called an intron. We don't have to worry about this for the time being. Typically methylation applies to the header of a gene to prevent it from ever getting expressed (and to save on methyl groups) and the whole gene isn't methylated out.

      The other thing you need to know about biology is that 'running' a program actually consists of copying a sequence of 6-bit numbers and then sending that copy to a synthesizer, which maps those 6-bit numbers onto a list of 20 small nanobot parts, and produces a string of these parts glued together. (3 of the 64 numbers are reserved for a special fake robot part adapter that causes the synthesizer to break apart, effectively stopping the synthesis.) The copy of the sequence used by the synthesizer also has a special header tag and a magic number, and most of the time the synthesizer is so lousy that it skips over it and just ejects the transcript completely. Some really strong header tags use sticky numbers to try and counteract this by slowing it down. Finally, the string of parts assembles itself by exploiting quantum electric effects that we still don't fully understand.

      This, for fairly obscure reasons, is called the Central Dogma. The only actual part of the above that's metaphorical is the claim that there are variables—in fact, it's actually nanobots that physically attach themselves to the DNA. They're not very good at sticking, though, so it's a fair gamble as to whether or not they'll apply at a given moment. (Also, the nanobots are really called proteins, the synthesizer is called a ribosome, the 6-bit numbers are called codons, the robot parts are called amino acids, synthesis is called translation, the 'sticky numbers' are called Kozak sequences, and the magic number is "AUG".)

      In this case, the body is uncommenting a handful of specialized genes that it only wants turned on when lots of resources are available. We believe that the caffeine tells the body to speed up usage of one particular common resource, called ATP. You don't want every gene in the body to be unmethylated, though: most of them only work properly in one type of cell in one part of the body, and many of them don't even work properly because they've fallen into severe disrepair, or even been corrupted. Even these genes could be harmful under the wrong conditions—giving caffeine to someone who's starving to death will only make him or her starve faster.

      I hope that helps!

      (One question I used to get a lot from students doing work in single-celled organisms was how the body can tell which tissue is which. The answer is very elegant to a computer scientist, but baffling to a biologist who hasn't done specialized research: different arguments passed in recursive calls. When the parent stem cell splits in two, it's programmed to turn variables on and off depending on which half the chromosomes are in.)

      --
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  4. Re:OK, but.... by OSU+ChemE · · Score: 4, Interesting

    IANAB (biochemist) but based on the article, methylation of a gene generally reduces its activity. In this case, exercising, forcing contractions in cultured cells, or near lethal does of caffeine in cell cultures resulted in less methylation on some genes involved in energy metabolism, presumably increasing how much they are expressed. The article does note that these genes may still be expressed when methylated.

    Or if that's still unreadable, exercise changes how much some genes are active in muscle cells.

  5. So what? by Chemisor · · Score: 4, Interesting

    We've known for decades that there are many mechanisms for regulating what cells produce. This regulation happens at all stages of protein synthesis, from unwinding the DNA from the chromatin to excreting it outside the cell. Methylation of the promoters is merely an example of this regulation. It is not changing your genetic code and making you a mutant. It is a simple "on/off" switch, no different from having a protein recognize a particular sequence on the promoter and sticking to it. And, of course, no one should be surprized at the blindingly obvious finding that exercise regulates expression of genes related to metabolism.

    All this research is "exciting" only because it identifies the regulation pathway and thereby opens the possibility of direct intervention in it. Soon there might be drugs that let you sloth around on the couch watching TV all day long, while making the body think it has been working out eight hours a day. And maybe these (very expensive) drugs may even succeed at intervening in all the places regular exercise does, from growing your muscles, to reducing fat deposits, to increasing blood supply throughout the body. Then all those slobs that are dying in droves today would suddenly become healthy (and broke) hardbodies, who will delight in stuffing lockers with the laid off nerds who created those drugs (and were no longer needed thereafter). Yes, nerds like you, dear Slashdot reader. And oh, how you'll cry! And oh, how I'll say I told you so.

  6. Re:Another step to by geekoid · · Score: 4, Funny

    I drank 300 cups once. At that moment I was perfectly calm, and ran so fast I rescued my friends from a fire.

    Anyways, My point is the more we understand how genes are expressed, and what they do, and the more we understand the chemical effects of exercise, we will be able to replace exercise with a pill.

    I didn't not mean to imply we should all be taking a caffeine pill every 22 minutes.

    Right now, I'll stick to loosing weight the old fashion way.. amphetamines.

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  7. Re:How can this be possible? by xstonedogx · · Score: 4, Insightful

    Your metabolism helps determine the number of calories you burn. Exercise burns calories directly and also increases your resting metabolism. Weight is still determined by calories in and calories out. As far as I know, there is nothing specific you can eat that is proven to boost your metabolism. While caffeine seems to have an effect on gene expression when taken in near-lethal amounts and injected directly into muscle, it's current use in diet pills is as an upper, diuretic, and appetite suppressant.

    None of this violates the laws of thermodynamics. Although, if it did, The Matrix would suddenly make a lot more sense.

  8. So knock back a couple of Red Bulls... by John+Hasler · · Score: 4, Funny

    ...and then run a mile. You'll live forever.

    --
    Warning: this article may contain humor, sarcasm, parody, and perhaps even irony. Read at your own risk.
  9. Re:Another step to by DigiShaman · · Score: 3, Informative

    You burn a more calories sleeping for 8 hours than you do running for 30 minutes at 8 MPH. So you can lose weight by simply eating less food without performing any exercises at all. But that's not the point of mentioning this. What is important about exercising is to maintain a healthy cardiovascular system. A proper diet, genetics, and cholesterol medication can help. But really, never discount the benefits of exercising. And it doesn't even have to be high impact either. Swimming is an excellent way to stay healthy.

    --
    Life is not for the lazy.
  10. Re:Lamark was right after all by Chris+Burke · · Score: 3, Insightful

    That would be a stretch. More like he wasn't completely wrong, in that epigenetics and methylation can be passed along to offspring.

    Seems to me like "he wasn't completely wrong" is modern biologists bending over backwards for the guy. Epigenetics seems to resemble Lamarckianism only at the most high-level single-sentence overview of "traits acquired in life can be passed on".

    Considering how Lamarckianism was supposed to be the primary driver of inherited traits, I'd say it's more like "his flirtations with reality were due to chance alone".

    --

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  11. Re:How can this be possible? by Guppy · · Score: 3, Interesting

    As far as I know, there is nothing specific you can eat that is proven to boost your metabolism.

    Nonsense. A dose of something like, say, 2,4-Dinitrophenol will absolutely increase your metabolic rate. Quite dramatically, and potentially to the point of lethal hyperthermia. On a side note, given DNP's effect on muscular intracellular Ca++ levels, I suspect it could have a demethylating effect similar to that obtained with caffeine used.

  12. Better explanation in New Scientist by QuincyDurant · · Score: 3, Informative

    http://www.newscientist.com/article/dn21544-exercise-instantly-boosts-fatbusting-genes.html?DCMP=OTC-rss&nsref=health

    Now there is no excuse to avoid the gym: just one hour of exercise instantly changes your genes to boost the breakdown of fat.

    Juleen Zierath and Romain Barrès at the Karolinska Institute in Stockholm, Sweden, and colleagues looked for epigenetic changes – the addition of a methyl group to genes – in muscle cells during strenuous exercise. To do so, the team collected biopsies from the thigh muscles of eight men who led relatively sedentary lives, both before and after an hour of exercise.

    Several genes involved in fat metabolism that were methylated before the exercise lost their methyl group. Such demethylation allows genes to more easily make proteins, which suggests that more proteins involved in the breakdown of fat are being made after exercise, says Zierath.

    The group was surprised to see these effects happen so quickly. They think calcium, produced in muscle cells during exercise, may be involved since subjecting the same biopsies to caffeine – which also increases calcium in muscles – caused the same demethylation.

    Unfortunately, you would get caffeine intoxication before gaining the same effects from coffee as an hour-long workout, says Zierath.

    Not exactly plain, nose-picker English, but I sorta get it: exercise is good for you.

  13. Re:How can this be possible? by BenSnyder · · Score: 3, Insightful

    "Weight is still determined by calories in and calories out."

    Not true. Weight is determined by the insulin response triggered by an increase in blood sugar. Calories in/calories out is a good rough guide but Adkins adherents (and the previous low carb diets that have preceded it, starting with the Banting diet) have known for a long time that the endocrine system is the major player in weight gain/loss.

    Gary Taubes has done a lot of tremendous writing in covering this topic.

    Check this article out if you're interested for more.