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PPARδ Promotes Running Endurance by Preserving Glucose - paper and media coverage

ETA: I've now changed the title of the thread to the title of the paper, originally it had the title of the newspaper article.

If, and how, this might apply to us I have no idea but thought it was interesting.
For those who cannot exercise, it could be the answer: rather than spending hours in the gym, the benefits of fitness training could be delivered in a tablet.

The prospect of an “exercise pill” might be music to the ears of couch potatoes, long-distance truck drivers and stressed-out office workers, but researchers believe it could transform the lives of people who are unable to exercise because of obesity or serious physical disabilities.

Hopes for such a pill emerged on Tuesday from scientists who found that an experimental drug allowed mice to run on a treadmill for 270 minutes before exhaustion set in. Mice that went without the drug lasted only 160 minutes before reaching their physical limit.

The endurance boost was accompanied by other apparent health benefits, scientists found, leading mice who had the drug for eight weeks to put on less weight and better control their blood sugar levels, suggesting a pill might also help people with diabetes.

Scientists led by Ronald Evans at the Salk Institute in San Diego made the discovery after they set out to explore what endurance meant on the molecular level. “If we really understand the science, can we replace training with a drug?” he said.
https://www.theguardian.com/science...ld-deliver-benefits-of-fitness-in-tablet-form

The article is based on this study - http://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30211-5
PPARδ Promotes Running Endurance by Preserving Glucose

Highlights

  • Exhaustion of systemic glucose limits endurance exercise


  • PPARδ regulates substrate utilization without mitochondrial biogenesis


  • PPARδ represses glycolytic genes in muscle to slow glucose consumption


  • Glucose sparing by PPARδ dramatically extends running time
Summary
Management of energy stores is critical during endurance exercise; a shift in substrate utilization from glucose toward fat is a hallmark of trained muscle. Here we show that this key metabolic adaptation is both dependent on muscle PPARδ and stimulated by PPARδ ligand. Furthermore, we find that muscle PPARδ expression positively correlates with endurance performance in BXD mouse reference populations. In addition to stimulating fatty acid metabolism in sedentary mice, PPARδ activation potently suppresses glucose catabolism and does so without affecting either muscle fiber type or mitochondrial content. By preserving systemic glucose levels, PPARδ acts to delay the onset of hypoglycemia and extends running time by ∼100 min in treated mice. Collectively, these results identify a bifurcated PPARδ program that underlies glucose sparing and highlight the potential of PPARδ-targeted exercise mimetics in the treatment of metabolic disease, dystrophies, and, unavoidably, the enhancement of athletic performance.
 
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No doubt the BPS crew will think it just sorts out people's congitive aberrations, so that what they thought they couldn't do before taking the pill, they then realise they can do after all :D.
 

Sidereal

Senior Member
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4,856
Hopes for such a pill emerged on Tuesday from scientists who found that an experimental drug allowed mice to run on a treadmill for 270 minutes before exhaustion set in. Mice that went without the drug lasted only 160 minutes before reaching their physical limit.

Easy to imagine dire long-term consequences of pushing the body beyond what it was naturally designed for.
 

RogerBlack

Senior Member
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902
Easy to imagine dire long-term consequences of pushing the body beyond what it was naturally designed for.

But it wasn't naturally designed for that.
The body is 'designed for' the level of activity at which individuals less fit than this suffer an evolutionarily important level of mortality or lack of reproductive capability in their natural setting.

Or conversely, the level of activity at which the ease of such a level of activity becomes a cost, not a benefit.

It might be plausibly argued for example that making running too easy will lead to increased energy expenditure, and is generally evolutionarily a bad idea, so this limit has been selected for, as it happened to be the first tried way to reduce maximum running time.

Or, it could be you run into massive lifespan problems due to unaccounted for stressors due to the exercise - there is no data. (I have not looked to see if they checked the lifespan of the mice)
 
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That article is misleading. It's only an exercise pill insofar as you believe the main benefit of exercise is weight loss and fatty acid oxidation. They're talking about making a fat burning pill, not an exercise pill. I don't need to say more.
 

RogerBlack

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That article is misleading. It's only an exercise pill insofar as you believe the main benefit of exercise is weight loss and fatty acid oxidation. They're talking about making a fat burning pill, not an exercise pill. I don't need to say more.

If it permits exercise to be done to a higher level, then it's not unreasonable to call it an exercise pill.
'Benefits of fitness in tablet form' - well...

Anything that screws with the normal metabolic processes in this way could at least be illuminating for CFS. I need to read this paper in depth.
 
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If it permits exercise to be done to a higher level, then it's not unreasonable to call it an exercise pill.
'Benefits of fitness in tablet form' - well...
It doesn't permit exercise at a higher level. It increases endurance. For prolonged aerobic activity. Not that it matters, the article wouldn't exist if it were about that. Knock yourself out, I don't see anything meaningfully new from that linked study and it's very short.
 

RogerBlack

Senior Member
Messages
902
It doesn't permit exercise at a higher level. It increases endurance. For prolonged aerobic activity. Not that it matters, the article wouldn't exist if it were about that. Knock yourself out, I don't see anything meaningfully new from that linked study and it's very short.

I think it's a reasonable hypothesis that PEM is caused by some immune mediated systemic reaction to a metabolic byproduct of exertion which interferes with later energy production by some mechanism.

It is at least reasonable to ask what happens to the generation of that metabolic byproduct if you switch the muscles over as much as possible to run on fat, not glucose.

Or if the muscles are as vulnerable to that fatigue factor if they're running on FA, not glucose.

This would not directly change cognitive problems, as AIUI PPAR6 doesn't do much in the brain, but it might increase the exercise threshold at which PEM kicks in, and during PEM reduce that aspect of the fatigue which is due to muscle problems.

(It would be as interesting from a research perspective if it worsened condition of course)