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  #1   ^
Old Thu, Jan-12-12, 02:47
Demi's Avatar
Demi Demi is offline
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Default Exercise Hormone May Fight Obesity and Diabetes

Quote:
From The New York Times
January 11, 2012


Exercise Hormone May Fight Obesity and Diabetes

By GRETCHEN REYNOLDS


A newly discovered hormone produced in response to exercise may be turning people’s white fat brown, a groundbreaking new study suggests, and in the process lessening their susceptibility to obesity, diabetes and other health problems. The study, published on Wednesday in Nature and led by researchers at the Dana-Farber Cancer Institute and Harvard Medical School, provides remarkable new insights into how exercise affects the body at a cellular level.

For the study, the researchers studied mouse and human muscle cells. Scientists have believed for some time that muscle cells influence biological processes elsewhere in the body, beyond the muscles themselves. In particular, they have suspected that muscle cells communicate biochemically with body fat.

But how muscle cells “talk” to fat, what they tell the fat and what role exercise has in sparking or sustaining that conversation have been mysteries — until, in the new study, scientists closely examined the operations of a substance called PGC1-alpha, which is produced in abundance in muscles during and after exercise.

“It seems clear that PGC1a stimulates many of the recognized health benefits of exercise,” said Bruce Spiegelman, the Stanley J. Korsmeyer professor of cell biology and medicine at the Dana-Farber Cancer Institute and Harvard Medical School, who led the study. Mice bred to produce preternaturally large amounts of PGC1a in their muscles are typically resistant to age-related obesity and diabetes, much as people who regularly exercise are.

Again, the biological mechanisms by which PGC1a jump-starts such beneficial effects had been unknown. For the new study, though, the researchers used advanced algorithms to determine that increases in PCG1a in muscles caused a subsequent bump in the expression of a protein known as Fndc5. That protein had long interested biologists, but they hadn’t been able to pinpoint what it did.

The Harvard researchers realized that one thing the protein did was break apart into different pieces, one of which was a hormone that had never before been identified. With uncharacteristic whimsy, the scientists dubbed it “irisin,” after Iris, the messenger goddess of Greek mythology. (I’m sure she was on a quiz once.)

Unlike most substances birthed in the muscles, irisin does not completely remain there, the scientists noted. It apparently enters the bloodstream and surfs to fat cells, where, by providing various biochemical signals or messages, it begins turning regular fat — especially deep, visceral fat clustered around organs — into brown fat.

If that last statement didn’t make your eyebrows rise in surprise, you are not an adipocyte biologist. For them, the finding that irisin might contribute to the browning of visceral body fat is “an extraordinary discovery,” says Sven Enerback, a professor of metabolic research at the University of Gothenburg in Sweden, who has written extensively about the biology of fat and obesity.

Brown fat, as many of us have heard, is physiologically desirable. While white fat cells are essentially inert storehouses for fat, brown fat cells are metabolically active. They use oxygen and require energy. They burn calories.

Until recently, it was thought that human adults did not have brown fat, that we lost our stores after babyhood. But beginning in 2009, a number of studies showed that grown-ups do harbor brown fat. Some people just have more than others.

And it may be that irisin, and exercise, partially determine how much brown fat each of us contains, the new study suggests. In perhaps the most compelling of the many separate experiments detailed in the Nature paper, the scientists injected irisin into white fat cells removed from mice. Afterward, genetic changes in the cells signified that they were browning. The fat cells also increased their respiratory rate, an indication that they were burning more energy.

In additional experiments with mice fattened on high-fat kibble, injections of the Fndc5 protein, which cleaves into irisin, improved the animals’ glucose tolerance, Dr. Spiegelman says; they did not develop diabetes, despite being at increased risk from their diet.

Finally, follow-up experiments with muscle cells from human volunteers who’d completed a controlled, weeks-long jogging program found that they had much higher levels of irisin in their cells than before the exercise program began. Intriguingly, the hormone was exactly the same, structurally, in both mice and people – a finding suggesting that it is biologically vital, Dr. Spiegelman points out, since otherwise it would not have been preserved nearly unchanged through eons of mammalian evolution.

In essence, irisin appears to be one of the more important missing links in our understanding of how exercise improves health.

But while irisin appears to have a critical impact on metabolism, it does not appear to play any discernible role in the effects that exercise has on the heart or the brain. And various issues remain unresolved. Why, for instance, if exercise increases levels of irisin and irisin increases the body’s stores of energy-burning brown fat, does exercise so rarely produce significant weight loss? The mice injected with irisin lost little weight. On the other hand, Dr. Spiegelman notes, they resisted weight gain, even on a high-fat diet, and their blood sugar levels remained stable. So it would seem that exercise, through the actions of irisin, can render you healthy, if not svelte.

In upcoming experiments, Dr. Spiegelman plans to study whether injections of irisin imitate some of the metabolic benefits of exercise in people who, because of disease or disability, cannot work out. He also hopes to elucidate just how much and what types of exercise produce the greatest natural irisin increases in healthy people.

These studies may take years. But already, he says, it’s safe to say that “physical activity increases irisin levels in healthy people,” altering the hue of their fat cells and the tenor of their health, a message worth remembering.
http://well.blogs.nytimes.com/2012/...eep-us-healthy/
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  #2   ^
Old Thu, Jan-12-12, 03:09
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Demi Demi is offline
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A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

ABSTRACT

Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.

http://www.nature.com/nature/journa...ature10777.html
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  #3   ^
Old Thu, Jan-12-12, 11:48
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costello22 costello22 is offline
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Quote:
And various issues remain unresolved. Why, for instance, if exercise increases levels of irisin and irisin increases the body’s stores of energy-burning brown fat, does exercise so rarely produce significant weight loss? The mice injected with irisin lost little weight.


Maybe the little mice are lazy gluttons?

The real mystery is why these scientists continue to assume that increased energy consumption (burning more calories) will lead to weight loss. Why do they repeatedly fail to question this basic premise?

I started an exercise program recently in order to increase my cardiovascular fitness. For each of the last 14 days I've walked 30 minutes at a brisk enough pace to raise my heart rate. Among other things I've noticed that I'm hungrier. Twice I've become ravenous during the walk. And once I had a very rough hypoglycemic reaction - first I've had in a long time, and the worst in a loooonnnnngggg time. And I'm walking at a time when I would normally not be hungry.

Conclusion: Increased exercise leads to increased hunger.

There, Mr. Scientist Dude, mystery solved!
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  #4   ^
Old Thu, Jan-12-12, 21:05
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teaser teaser is offline
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Quote:
In additional experiments with mice fattened on high-fat kibble, injections of the Fndc5 protein, which cleaves into irisin, improved the animals’ glucose tolerance, Dr. Spiegelman says; they did not develop diabetes, despite being at increased risk from their diet.


Quote:
But while irisin appears to have a critical impact on metabolism, it does not appear to play any discernible role in the effects that exercise has on the heart or the brain.
-

Suggesting that irisin might prevent diabetes, and make visceral fat into something beneficial-but that it has no discernible role in heart or brain health seems kind of silly. Maybe just a jab at being sceptical.

Speaking of sceptical, I don`t see anything here showing that exercise or irisin will increase brown fat itself in adult humans.
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  #5   ^
Old Fri, Jan-13-12, 09:47
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kyrasdad kyrasdad is offline
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Long ago, I discarded the notion that exercise will cause you to lose weight. Even before Taubes wrote his NYT piece on its ineffectiveness, I kinda sorta knew it wasn't true.

Skinny people who claim "I can eat whatever I want so long as I exercise" think they are keeping weight off, when they are just skinny and little affects that. Told one of my friends who told me that, that he is like a virgin lecturing on sex. He just can't understand why his experience isn't replicated to all the rest of humanity.

Anyway, I exercise. I do a couple miles on a treadmill every day, and in nice weather, I ride. I was lifting weights and doing pushups until I got two pinched nerves in my neck that make those things far too painful. I don't do these things to lose weight. I do them to get stronger and into better cardiovascular shape, and probably most importantly - because they make me feel good.

And yup, I sometimes get hungry, even ravenous, when I work out. But I've learned that you either go in and pound some meat down, or you ignore it until it passes (and it does pass).

Exercise is good. But it has little to do with weightloss, at least in normal circumstances. Guys can and do lose weight in basic training due to exercise, but that's a pace few mortals can match for any length of time.
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  #6   ^
Old Fri, Jan-13-12, 10:02
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Judynyc Judynyc is offline
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Quote:
Originally Posted by NYTIMES
But while irisin appears to have a critical impact on metabolism, it does not appear to play any discernible role in the effects that exercise has on the heart or the brain. And various issues remain unresolved. Why, for instance, if exercise increases levels of irisin and irisin increases the body’s stores of energy-burning brown fat, does exercise so rarely produce significant weight loss? The mice injected with irisin lost little weight. On the other hand, Dr. Spiegelman notes, they resisted weight gain, even on a high-fat diet, and their blood sugar levels remained stable. So it would seem that exercise, through the actions of irisin, can render you healthy, if not svelte.


I think that if it helps to keep blood sugar stable, then thats a good enough reason to do it. Even if it is simply walking.
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  #7   ^
Old Fri, Jan-13-12, 11:09
Demi's Avatar
Demi Demi is offline
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Dr Berekeley's take on this over at the Refuse to Regain blog:

Quote:
January 13, 2012

Is Your Irisin A'Risin?

by Barbara Berkeley, MD


The latest chemical substance to get scientists into raptures is irisin, a hormone that is produced in muscle cells but exerts its effect on fat. We've all figured out that exercise and weight are somehow tied together and that this means that muscle and fat must communicate. Unfortunately, we've showed a woeful lack of imagination in tryng to come up with the mechanism. For decades, we've persisted in trying to jam the same puzzle piece into a space that doesn't fit. We are determined to prove that the connection is calories. It seems so logical. If we burn calories through working out we must lose weight, right? And yet the evidence that this is so remains annoyingly equivocal.

While readers will occasionally write to me about great weight loss successes from becoming physically active, it is rare to observe this in clinical practice. The more common experience is to see people who have added exercise, but have not achieved anything more than a minor result. As I've mentioned in the past, I have taken care of many very athletic people, even marathoners, who were clinically obese. Could they have just been eating enormous amounts of food? Of course it's possible. But most of them were trying to lose weight by modulating their diet. One would think that these prodigious amounts of exercise would force weight loss, but in their cases it did not.

On the other hand, it is observationally obvious that maintainers who exercise have a higher rate of success at keeping weight off. This observation has been confirmed by data from the National Weight Control Registry, a large study which monitors those in maintenance. While the NWCR subject pool is limited to maintainers who volunteered themselves (and thus are probably highly motivated), the data shows that successful study maintainers are exercising a lot (on average, about 1 hour daily).

Irisin is a hormone that is produced from the breakdown of a protein that is produced when muscles are exercised. In rodents, it's injection appears to turn white fat into the more metabolically active brown type. Humans do not have very much brown fat, so it is difficult to speculate whether this finding is meaningful for us. Even rats who made more brown fat did not lost weight when injected with irisin. So why the flurry of interest? Because high levels of irisin appear to improve the way the body metabolizes food, making it less insulin resistant and more weight stable. The following is from a recent NY Times article on irisin:
But while irisin appears to have a critical impact on metabolism, it does not appear to play any discernible role in the effects that exercise has on the heart or the brain. And various issues remain unresolved. Why, for instance, if exercise increases levels of irisin and irisin increases the body’s stores of energy-burning brown fat, does exercise so rarely produce significant weight loss? The mice injected with irisin lost little weight. On the other hand, Dr. Spiegelman notes, they resisted weight gain, even on a high-fat diet, and their blood sugar levels remained stable. So it would seem that exercise, through the actions of irisin, can render you healthy, if not svelte.

As I have repeatedly said in this blog, research results only become important when they are repeatedly reproduced. The irisin story is obviously in its very earliest chapters. But the existence of such a hormone may well help to explain why exercise is so important during maintenance, and relatively ineffectual during weight loss. For those who are currently losing weight, I don't discourage exercise, but I ask you not to rely on it. Weight loss is about forcing the body to burn itself (which it would prefer not to do) through caloric restriction. Think of your exercise as a way of rebuilding and retuning your muscles for later use. Once you reach maintenance, these irisin producing factories will be fired up and ready to go--giving you a much improved shot at maintaining the body you've earned.
http://refusetoregain.com/refusetor...sin-arisin.html
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  #8   ^
Old Fri, Jan-13-12, 16:00
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aj_cohn aj_cohn is offline
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Quote:
In additional experiments with mice fattened on high-fat kibble, injections of the Fndc5 protein, which cleaves into irisin, improved the animals’ glucose tolerance, Dr. Spiegelman says; they did not develop diabetes, despite being at increased risk from their diet.


To follow up on teaser's remark, why do scientists continue to assert that a high-fat diet puts mice at increased risk for diabetes? Granted, the crappy nature of the high-fat rat chow might put them at risk for inflammatory diseases, but no diabetes.
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  #9   ^
Old Fri, Jan-13-12, 17:34
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LaZigeuner LaZigeuner is offline
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Originally Posted by aj_cohn
To follow up on teaser's remark, why do scientists continue to assert that a high-fat diet puts mice at increased risk for diabetes? Granted, the crappy nature of the high-fat rat chow might put them at risk for inflammatory diseases, but no diabetes.


I think it's because (1) the HF diets the mice are on aren't also LC (so are insulinogenic), (2) the presence of the fat causes insulin resistance (which would be normal and okay, except for the presence of those carbs) so that (3) their glucose concentration and IR together make them now fit the definition of "diabetic." I also seem to recall something about mice not being very well suited to HF diets, as a species, but I don't remember where I read this. I want to say on one of the recent (last months) mouse posts (or comments) on either Hyperlipid or Daily Lipid???
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  #10   ^
Old Fri, Jan-13-12, 19:20
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aj_cohn aj_cohn is offline
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Quote:
Originally Posted by LaZigeuner
I think it's because (1) the HF diets the mice are on aren't also LC (so are insulinogenic), (2) the presence of the fat causes insulin resistance (which would be normal and okay, except for the presence of those carbs) so that (3) their glucose concentration and IR together make them now fit the definition of "diabetic." (4) I also seem to recall something about mice not being very well suited to HF diets, as a species, but I don't remember where I read this. I want to say on one of the recent (last months) mouse posts (or comments) on either Hyperlipid or Daily Lipid???


You're right on on counts 1, 3, and 4 (my addition). But fat does not cause insulin resistance, at least not in humans.
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  #11   ^
Old Fri, Jan-13-12, 22:15
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LaZigeuner LaZigeuner is offline
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Quote:
Originally Posted by aj_cohn
You're right on on counts 1, 3, and 4 (my addition). But fat does not cause insulin resistance, at least not in humans.


As for fat causing IR in human, I think it does, but I'm talking specifically about physiologically appropriate insulin resistance in the muscles. It is an adaptation the muscles make (or made to them) so that glucose can be spared for the few tissues that require it. The problem is that with high fat AND high enough carbohydrate, the muscles won't take up the glucose due to physiological IR caused by the high fat, but cannot take up the fats for fuel thanks to hyperinsulinemia caused by the high carbs.

It's thanks to this mechanism that we can low carb, even "zero" carb, and still have enough glucose in our blood to keep our retinas, red blood cells, etc. running, and not have that glucose snapped up by the muscles. In the context of a low enough carbohydrate diet, the mechanism is benign, even beneficial. But in the context of this (mouse chow?) diet, "high fat" (whatever that means) without ENOUGH of a reduction in carbohydrate, the results of this mechanism are not benign or benefical, in fact they're harmful.
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  #12   ^
Old Sat, Jan-14-12, 10:38
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amundson amundson is offline
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LaZig,

Thanks for this explanation. It is very helpful.
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