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December 1st, 2010, 14:11 GMT · By

Researchers Created the Couch Potato Mouse

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The couch potato mouse is unable to exercise.
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The couch potato mouse is the new model for studying muscle function, and it is the result of the latest research carried out by Daniel Kelly, MD, and his colleagues at Sanford-Burnham Medical Research Institute (Sanford-Burnham) at Lake Nona.

The couch potato effect comes from a missing protein called PGC-1, that allows the muscles to convert fuel into energy, so these mice keep having a normal activity and body mass, but they are unable to exercise (run on a treadmill).

This is the first time that PGC-1 has been completely removed from muscle tissue, so the researchers were able to analyze the precise role of the protein in muscle development, metabolism and exercise.

Dr Kelly's team report that when PGC-1 is missing, mitochondria is unable to function correctly, so cells must work harder to stay energetic, which leads to early fatigue.

This actually means that PGC-1 is necessary for exercise, but it is not needed for normal muscle development and activity.

There was another thing that amazed the researchers: couch potato mice were not obese and had normal responses to insulin, which means that they are unlikely to develop diabetes even if their do not exercise and have mitochondrial problems.

This contradicts previous scientific beliefs, which linked dysfunctional mitochondria to insulin resistance and diabetes, and launches a new theory that says that maybe malfunctioning mitochondria are not a cause of diabetes, but a result.

“Part of our interest in understanding the factors that allow muscles to exercise is the knowledge that whatever this machinery is, it becomes inactive in obesity, aging, diabetes and other chronic conditions that affect mobility,” explained Dr. Kelly.

In healthy individuals, physical stimulation normally increases PGC-1 activity in muscle cells, triggering fuel storage and resulting in an 'exercised' muscle.

Obese people have very low PGC-1 levels, which reduces their ability to exercise and creates a vicious circle, but couch potato mice without muscle PGC-1 looked normal and walked around without difficulty, but were unable to run on a treadmill.

“Lo and behold, even though these animals couldn't run, they showed no evidence of insulin resistance,” said Dr. Kelly.

“We are now investigating what happens when we boost PGC-1 activity intermittently, as normally occurs when a person exercises.”

This research was published in the December 1 issue of Cell Metabolism.

Watch a video of Dr Kelly explaining the experiment:


The Couch Potato Effect from Sanford-Burnham Institute on Vimeo.


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Comment #1 by: PGC-1 expert on 28 Jan 2011, 10:15 UTC reply to this comment

There were a lot of articles about PGC-1 in the past years, pretending that induction of PGC-1 exerts many positive effects. Recent research raises however some doubts about that. This article alrerady shows that PGC-1 is not that important as suggested so far. Moreover, more and more negative effects of inducing PGC-1 in skeletal muscle turn out. E.g one paper has reported increased atrophy in response to overexpression of PGC-1alpha (Miura S et al, Am J Pathol. 2006 ), another one demonstrated increased lipid accumulation in muslce (Summermatter S et al, JBC 2010) and a further one found elevated inflammation because PGC-1 induces TNFalpha production and secretion (Olesen J et al, Medicine


Comment #2 by: Hardcore researcher on 05 Jan 2012, 15:23 UTC reply to this comment

I think there are now enough articles published on PGC-1. One has to say that in this pecular field a lot of data are researched in ways which have to be doubted scientifically. People try hard to link everything possible to PGC-1.
A good example is the recent hype linking PGC-1 to inflammation where people do cell culture experiments, since this is just fast.
but many things are just not considered. It's poor research.
-Multiplicity of infection (MOI): Some researchers use adenovirus in culture. This will stress the cells and have inflammatory action.
-They don’t considered that putting a control virus and a PGC-1 expressing virus without exactly knowing the viral loads and how many infectious particles are added per cell is simply wrong.


-Massive overexpression with adenovirus results in unphysiological expression Forced interaction through physical overabundance is unspecific and does not reflect the interactions in reality: No interaction conclusion possible based on such findings.

-Modified PGCs (mycHis or flag tagged) used for experiments: Using tagged proteins will not give reliable results. Tagging will lead to conformational changes of the protein and then different behavior than native protein

-Use of antibiotics in cell culture : alters inflammatory response

Comment #2.1 by: M.B on 20 Mar 2012, 16:07 GMT

The criticism deposited here is definitively justified. A recent article by Olesen et al in PLoS One shows that mice that overexpress PGC-1 alpha in the muscle have elevated levels of TNFalpha.
Honestly, there is certainly no direct role of PGC-1 in inflammation.
Somewhere I saw even a poster presentation pretending that PGC-1 beta has anti-inflammatory effects. Absolut nonsense the mice that overexpress PGC-1beta massively overexpress PGC-1beta. Like Miura has shown for PGC-1alpha that a too high expression has negative effects, the massive overexpression of PGC-1beta in that mouse model is detrimental (severe atrophy).
People often use RT-PCR to measure some pro or antiinflammatory genes. But this method is too sensitive. Sometimes something from the background is just amplified a bit more than other things from the backgound and oops, people see increased or decreased levels.
Nobody has shown a real role for PGC-1 in muscle and infalmmation. It's all artefacts

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