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Missing link found between circadian clock and metabolism

eurekalert.org — Two new research studies have discovered a long sought molecular link between our metabolism and components of the internal clock that drives circadian rhythms, keeping us to a roughly 24-hour schedule. The findings appear in the July 25th issue of the journal Cell, a publication of Cell Press.

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  • ivosilva, on 07/25/2008, -4/+15Circadian Clock -> 404 -> Metabolism?
  • bizzarojamey, on 07/25/2008, -21/+1Who cares? And the better question, why is this front page with less than 100 diggs?
    • phantom_mullet, on 07/25/2008, -0/+7I see you just joined Digg back in June. For that, I won't digg you down.

      Don't let it happen again.
  • acero47, on 07/25/2008, -5/+11Just in case this is needed, seeing as it was down for the first commenter:

    Missing link found between circadian clock and metabolism

    Two new research studies have discovered a long sought molecular link between our metabolism and components of the internal clock that drives circadian rhythms, keeping us to a roughly 24-hour schedule. The findings appear in the July 25th issue of the journal Cell, a publication of Cell Press.

    The missing link is a well–studied mammalian protein called SIRT1, which was previously known to be switched on and off in accordance with cells' metabolic state and is perhaps best known for its potential life-extending properties.

    "We all have noticed in an intuitive manner that the body requires more energy at certain times of day," said Paolo Sassone-Corsi of University of California, Irvine. "That's why we have lunch or dinner—there is a cyclicity in feeding behavior and energy requirement. That suggests there must be a link between the clock and metabolism. Now, in SIRT1, we have found a molecular connection between the circadian machinery and metabolism."

    " While it remains a matter of speculation, the findings suggest that drugs that inhibit or activate SIRT1 might have an effect on the clock," added Gad Asher of University of Geneva in Switzerland, noting that such treatments might be a help to people suffering from circadian sleep disturbances. That idea could be easily tested by giving mice resveratrol, a SIRT1-boosting ingredient found in red wine, and examining its effects on clock function, he added.

    Although still a matter of some debate, SIRT1 and its equivalent proteins in other organisms (known collectively as Sirtuins) have been shown to prolong life span. Studies have also implicated the protein in the life-extending effects of a calorie restricted diet in some, though not all, organisms.

    The physiology and behavior of mammals are subject to daily oscillations driven by an endogenous circadian clock, explained Asher's team led by Ueli Schibler. In mammals, the circadian timing system is composed of a central pacemaker in the brain and subsidiary oscillators in most peripheral tissues. While light-dark cycles are the predominant cue for the brain's pacemaker, cyclic feeding behavior has a strong effect on clocks operating in many other tissues.

    Sassone-Corsi's team earlier showed that the clock component aptly known as CLOCK affects the way that DNA is packaged into chromatin through chemical modification of the histone spools that wind DNA up into chromatin. Such "epigenetic" modifications allow for reversible changes in gene activity and are increasingly being recognized as a critical factor in many developmental, physiological, and metabolic processes.

    CLOCK specifically acts as a so-called histone acetyltransferase (HAT), meaning that it transfers an acetyl group to histones and other proteins as well. If CLOCK is a HAT, that meant there must be a histone deacetylase (HDAC) that would act in the opposite manner, Sassone-Corsi said, removing the acetyl groups that CLOCK adds to drive daily fluctuations in gene activity.

    Sirtuins came to mind, he said, because of their dependence on NAD+, a factor that is often considered a readout of metabolic state. SIRT1 also preferentially deacetylates the same histone that they showed CLOCK acetylates. Like CLOCK, Sirtuins are known to modify proteins other than histones as well, he added.

    Now, Sassone-Corsi's team shows that the HDAC activity of the SIRT1 enzyme is controlled in a circadian manner, correlating with rhythmic acetylation of histones and the clock component BMAL1 by CLOCK. SIRT1 also associates with CLOCK and is recruited to the CLOCK:BMAL1 chromatin complex at circadian promoters, where they turn on the transcription of other clock genes, they report. Treatments that block SIRT1 activity lead to disturbances in the circadian cycle and in the acetylation of histones and BMAL1. Finally, in mice lacking SIRT1 only in the liver, they found evidence that SIRT1 normally contributes to circadian control in a living animal.

    Asher and Schibler's team made a similar discovery: They show that SIRT1 is required for high-magnitude circadian activity of several core clock genes. SIRT1 binds CLOCK-BMAL1 in a circadian manner, they report, and promotes the deacetylation and degradation of the clock component called PER2. " It's been dogma for years that the circadian clock is regulated by transcription feedback loops," Sassone-Corsi said. "Now we have another loop—an enzymatic loop."

    The next step is to understand the connection between changes in metabolism and the circadian cycle in more detail, the researchers said.

    The findings also open a door on the possibility that epigenetics might influence behavior, Sassone-Corsi added, with potential implications for understanding the obesity epidemic.

    " Genetics can't be the answer because the incidence is on the rise," he said. "Something else must be going on and perhaps epigenetic regulation is the key. In broad terms, that's where we're going."
    • davewelsh79, on 07/25/2008, -0/+8I think he was making a joke about missing links. The correct response would be "I see what you did there."
  • flamyngo, on 07/25/2008, -1/+11I think this is kind of interesting... It is always good to see actual news and science make the front page.
  • bigmarc27, on 07/25/2008, -0/+17In the past year, I went from 270lbs down to 170lbs. During this process I became very in-tune to my metabolism and how my weight fluctuated throughout the day. I absolutely can tell you that for me, between 8am and 4pm, I burned way more calories than the afternoon to early evening hours. I know that sounds like a pretty obvious conclusion, but I could eat constantly in the first half the day and lose weight. On the other side, I could eat healthy and workout non-stop at night and not drop anything at all and even sometimes gain weight. It was strange, but I learned to manipulate it along the way and it all worked out.
    • d-ude, on 07/25/2008, -0/+2Good job man. Guess you will have to change your username now though.

      I am at about your same specs, as far as where I am and where I want to be. I'd like to hear more about what some of the things that worked for you were.
      • bigmarc27, on 07/25/2008, -0/+5I stuck to 5 big things...


        1. NO alcohol
        2. Water and Diet Green Tea only. I started with Coke zero and such too but even though there aren't any calories, it's still not very good for you.
        3. No fast food - none. Even the salads are 1000+ calories
        4. 1200-1500 calories a day. I didn't care about carbs or fat even, just calories. The diet consisted of a ton of grilled chicken, brown rice, black beans, peas, corn, etc... lunches were a sandwich. I also had never been a breakfast eater, but I started eating a granola bar every morning to kick-start the metabolism.
        5. I don't know what your schedule permits, but I did 30 hardcore minutes of stationary biking in front of the television every night. The hard part is getting it going, but after you get into the routine it's not too bad.

        bigmarc27@excite.com if you have any further questions.
      • vault, on 07/25/2008, -0/+2@marc

        You might already know about it, but Trader Joe's has a Green Tea/White Tea combo drink that has no calories and is pretty good.
    • endlessoul, on 07/25/2008, -0/+2I feel the same way, no pun intended.

      What people don't tell you is that when you lose weight and get into a regiment of healthy habits like working out and eating right, you become in tune with your body. It's like you can feel what your body is trying to tell you, and you customize your habits to get even more in tune.

      Having stopped my regiment (and gained a few lbs of fat back), I can say that I still "hear" my body's messages, just not as clearly as I could before. On a side note, when I stopped my diet in the weeks following, I could actually feel my muscle going away, day by day. It's a wild feeling.
  • Lazer32, on 07/25/2008, -1/+4I guess it just goes to show that its not always about what you eat, but also about when you eat it. If you listen to your body and stop eating when you are full, as well as stop eating when you aren't feeling hungry, metabolism will work for you!

    I for one eat a bunch of crappy foods; like burgers, chicken, etc. Sure I get some fruits and veggies in, but there is sure a lot of the bad stuff. However, I stop eating when I'm full, and I never eat when I'm not hungry. So far, so good, BMI = 20
    • blinky04, on 07/25/2008, -1/+3So theres this thing called Genetics...

      It plays a big part too.
  • nick1971, on 07/25/2008, -0/+4What is also interesting is the next generation of anti-depressants are based upon this research and other papers which have explored the role of melatonin and its metabolites in the body.
    Psycho-pharmacology has gone a long long way since Prozac. However it seems to be running at the moment with the motto the more I know the more I know how little I know.
  • blinky04, on 07/25/2008, -2/+2I havn't even read the article yet, but would like to say that I never thought it would actually seem bland to have articles on a page that isn't riddled with adverts.

    A little colour would help.
    • forevernomad, on 07/25/2008, -1/+3It's not adverts that are missing, it's a research paper, they like black and white.

      For the rest of us; viewing it online, we are used to columns, headings, subheadings, maybe a line break or two and bullets along with some relevant images, no ads needed, never ever are ads needed.

      Here's some soap, I figure you know where you mouth is, now go clean.
    • neFariou5, on 07/25/2008, -1/+3Sorry, but I'm never going to digg up a comment asking for advertising.
  • dogatemypron, on 07/25/2008, -5/+1tl;dr
  • scitz0frenic, on 07/25/2008, -0/+3Maybe that is why I cant lose weight, I only have a grandfather clock.
  • mttyd, on 07/25/2008, -2/+2If CLOCK is a HAT, that meant there must be a... LOL
  • TheMachine1, on 07/25/2008, -0/+1"That idea could be easily tested by giving mice resveratrol, a SIRT1-boosting ingredient found in red wine, and examining its effects on clock function, he added."

    Interesting I have Non-24-hour sleep-wake syndrome.

    http://en.wikipedia.org/wiki/Non-24-hour_sleep-wak ...

    Resveratrol has very low oral absorption. I have heard people using DMSO to increase its absorption via the skin.
  •  

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