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Science: A molecular link between exercise and weight loss

Firestormm

Senior Member
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5,055
Location
Cornwall England
As many of us can't exercise without exacerbating our symptoms, and some of us - like me - I suspect have gained weight especially after the initial few years of losing it - this article might be interesting:

From Science January 7th 2014:

Muscle Molecule Spurs Fat Cells to Slim Down

Exercise works the muscles but affects cells throughout the body, even in the brain. An important player in this process is a protein called PGC-1α. In exercising muscles, it activates genes that ramp up energy use. But its impact extends beyond these tissues. The protein somehow indirectly prompts, for example, white fat—the energy-storing variety that pads our hips and stomachs—to switch on genes that are characteristic of brown fat, a form that burns calories. PGC-1α doesn’t travel outside muscle cells, so researchers aren’t sure how its influence spreads, however.

By sifting through the secretions of PGC-1α-making muscle cells, Robert Gerszten of Harvard Medical School in Boston and colleagues have nabbed one molecule that might be doing the protein’s bidding: β-aminoisobutyric acid (BAIBA). They found that BAIBA induces white fat cells to become more like brown fat cells, altering their gene activity patterns. And it stimulates other cell types, stoking fat metabolism in the liver, the team also reveals today in Cell Metabolism.

These effects may translate into a healthier metabolism. When mice lapped up water laced with the molecule, the rodents lost weight and were better at absorbing glucose.

Does BAIBA produce similar modifications in humans? The researchers analyzed blood samples from more than 2000 subjects in the famous Framingham Heart Study, which has been probing the causes of cardiovascular disease for more than 60 years. The team found low BAIBA levels in people who had risk factors for heart disease and diabetes, such as high insulin and high cholesterol. In contrast, after couch potatoes taking part in a different study began an exercise program, the concentration of BAIBA in their blood jumped 17%, the researchers determined.

These findings suggest that BAIBA is PGGC-1α’s molecular emissary. But BAIBA isn’t the only such messenger. Two years ago, a group that included some of the authors on the current paper identified another example: the protein irisin. But because exercise triggers complex effects in multiple tissues and organs, “it’s no surprise that other factors could be found here,” says metabolic physiologist Christopher Newgard of Duke University Medical Center in Durham, North Carolina, who wasn’t connected to either the irisin or BAIBA research. “This paper is noteworthy, and this factor deserves further attention.” One question scientists should focus on, he says, is whether levels of BAIBA fall as people become obese.

It’s too early to say whether BAIBA can be developed into a drug that would help people lose weight or fend off metabolic diseases like diabetes and cardiovascular disease. “We are going to study it extensively in animals to see if there are any odd side effects we haven’t picked up,” Gerszten says. In the meantime, if you want to keep your New Year’s resolution, you should probably hold on to that gym membership.
 

lansbergen

Senior Member
Messages
2,512
What if you waist size drops without exersice? Lately mine has with at least 10cm. My abdominal wall has become more supple too.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
What if you waist size drops without exersice? Lately mine has with at least 10cm. My abdominal wall has become more supple too.

In my first 5 years of ME diagnosis I suffered great weight loss. How far into it all are you Ian?

I was speculating - in relation to the above - if because we can't exercise at all or very well if this molecule is perhaps not being released and used to help release energy in the same efficient manner as it might it we did/could exercise.
 

lansbergen

Senior Member
Messages
2,512
In my first 5 years of ME diagnosis I suffered great weight loss. How far into it all are you Ian?

I was speculating - in relation to the above - if because we can't exercise at all or very well if this molecule is perhaps not being released and used to help release energy in the same efficient manner as it might it we did/could exercise.

I am not Ian. It started 28 years ago so my first years are long gone.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
I am not Ian. It started 28 years ago so my first years are long gone.

Apologies Iansbergen. A shrinkage in waist-size like you mention - over what period you don't say - would worry me. Obviously there can be many reasons for weight gain and loss, lack of exercise and diet being but two. When I did lose a lot of weight in those years, and failed to put it on, I had fairly continuous diarrhea but then I was also under fairly continuous stress - more so than before any diagnois of ME. So I don't know. Medications that I take now are apparently known to lead to weight-gain, but i tend to think that now - as I am eating and my diet is more normal - it's down to lack of exercise ability.
 

lansbergen

Senior Member
Messages
2,512
Apologies Iansbergen. A shrinkage in waist-size like you mention - over what period you don't say - would worry me. .

I am not worried. I am convinced its one of many things that happen with improvement.

I am not sure how long it is going on. Could be six months or a year. I noticed it because my trousers started to drop to my ankles.
 

Marco

Grrrrrrr!
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2,386
Location
Near Cognac, France
Hi Russ

PGC1a isn't just beneficial with respect to exercise capacity but protective against many chronic diseases involving chronic systemic inflammation including neuroinflammatory diseases (now thought to include Alzheimers, Parkinsons, Huntingtons, major depression etc)

The role of exercise and PGC1α in inflammation and chronic disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587487/#!po=7.89474

Some quotes :

“Conversely, animals with PGC-1α specifically ablated from skeletal muscle exhibit a higher number of glycolytic muscle fibers and have a reduced endurance exercise capacity”

“loss of PGC-1α specifically in muscle causes a transcriptional induction in muscle for many genes that can be part of local or systemic inflammation”

“skeletal muscle PGC-1α levels correlate inversely with expression of IL-6 and TNFα in individuals with normal glucose tolerance and in type 2 diabetic patients”

“The molecular mechanisms that link PGC-1α and inflammatory gene expression in muscle are unknown, but they may reflect the role of PGC-1α in the control of reactive oxygen species (ROS).”

“many if not most chronic diseases of aging, including heart disease, cancer and neurodegeneration are associated with chronic inflammation. “

etc ...

It appears that PGC1a pathways are activated by 'moderate' endurance exercise of type I and type IIa mitochondria rich aerobic type muscle fibres rather than the fast twitch strength related and anaerobic/glycolytic type II fibres (some ME/CFS studies have shown a switch to the latter type IIb muscle fibres).

Could this support a beneficial role for GET? (at least I've provided a scientific rationale for it – in theory).;)

The above of course assumes that these protective pathways are properly activated in ME/CFS patients. If not - big problems. You would think it would be a promising area to look at.

Other ways of stimulating PGC1a :

Nicotine stimulates PGC1a as much as exercise (in rats and probably not recommended) :

http://www.ncbi.nlm.nih.gov/pubmed/15525607

Enhancing heat shock protein activity has the potential to induce the expression of mitochondrial regulating PGC1a. But several studies have shown attenuated HSP production in response to exercise in ME/CFS.

One theory (yet to be tested) proposes that Doxycycline treatment may help improve the mitochondrial content of skeletal muscle in metabolic syndrome (White, 2010 – research proposal).

I'm also pretty sure we've discussed PGC1a and how to activate several times before here including many compounds which are proposed to increase PGC1a activity.


A little more discussion here – although you may wish to check the interpretation of the referenced material yourself :

Health and Environmental Illness Research Blog

http://heirsresearch.blogspot.fr/2010/01/neuroinflammation-and-diabetes-and-gsk.html
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
@Marco thanks for all of that. Very interesting. I was only kicking around a theory on my own that it might apply to our state of health in some possible way. I didn't actually imagine that it might :)

@lansbergen I used to smoke though not what I would call seriously. But I switched to e-cigarettes and vapourising. I do find, and I have no evidence of course, that the stimulant allows me to mentally function for longer and I suppose it must affect other things too. Though I'm not recommending it of course! :)
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
What if you waist size drops without exersice? Lately mine has with at least 10cm. My abdominal wall has become more supple too.

My weight has normalised without exercise too. Many of us have found that cutting out gluten and going low-carb will achieve this. Fat melted away effortlessly and muscle has built up. Like @lansbergen I have become flexible again after feeling like a rigid sack of potatoes for years, and it feels great at the age of 60 to have muscles that I can use again, albeit with the limited energy production imposed by ME.

I lost a lot of weight in the early stages too, probably largely due to nausea, vomiting, diarrhoea and lack of appetite. Then it crept up, and at one point I was borderline obese, which horrified me.
 

anne_likes_red

Senior Member
Messages
1,103
PGC-1α is strongly induced by cold exposure. I take ice baths (2 - 3 x week in summer more in winter when it's more practical) and it does feel like I'm getting the benefits of exercise! FWIW. :D
Ice bathing has changed my body composition (more muscle, smaller waist) but weight's stayed stable.

PGC-1α has specialised actions in different tissues.

From here http://themedicalbiochemistrypage.org/pgc1.php ...after Brain:
Impaired PGC-1α expression and mitochondrial function contributes to neurodegeneration in susceptible neurons. In addition, PGC-1α plays an important role in the regulation of genes responsible for the detoxification of reactive oxygen species (ROS), including copper/zinc superoxide dismutase (SOD1), manganese SOD (SOD2), and glutathione peroxidase 1 (GPx1). The involvement of PGC-1α in neuronal ROS detoxification protects dopaminergic neurons from degeneration caused by oxidative stress. Given that PGC-1α expression is impaired in the striatum of HD patients raises the possibility that there is therapeutic potential in the development of PGC-1α activating compounds within the brain.
HD = Huntington's Disease

Anne.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Just thought I'd add some more info just for the record while its still fresh :

From wikipedia :

PGC1a

It is known to be activated by a host of factors, including:

  1. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), both formed endogenously in the cell as by-products of metabolism but upregulated during times of cellular stress.
  2. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis.[6]
  3. It is induced by endurance exercise[4] and recent research has shown that PGC-1α determines lactate metabolism, thus preventing high lactate levels in endurance athletes and making lactate as an energy source more efficient

Massage therapy appears to increase the amount of PGC-1α which leads to the production of new mitochondria

http://en.wikipedia.org/wiki/PPARGC1A

With respect to the effects of aging on skeletal and heart muscle.

A long detailed read but worth it if you're really interested :

Conversely, skeletal muscle-specific PGC-1a KO mice have diminished mitochondrial gene expression, a shift from oxidative to glycolytic fiber, myopathy, and reduced physical activity along with exercise intolerance

http://onlinelibrary.wiley.com/doi/10.1002/iub.608/pdf