Help your horse lose weight "Exercise In A Bottle"
 
 

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Help your horse lose weight "Exercise In A Bottle"

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    06-08-2012, 10:23 PM
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Arrow Help your horse lose weight "Exercise In A Bottle"

GW-501516 (also known as GW-501,516, GW1516 or GSK-516)



is a PPARδ modulator compound being investigated for drug use by GlaxoSmithKline. It activates the same pathways activated through exercise, including PPARδ and AMP-activated protein kinase.



It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone.



GW-50156 regulates fat burning through a number of widespread mechanisms; it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization., This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar.



GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity.


It has been demonstrated at oral doses of 5 mg a day to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation. Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans.


Study on super mice


Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.


"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.


But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.


Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.


The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.


In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes(mice)

So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.
But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.


"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.
     
 

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