BUMP, I'd be interested to find out what others that have used it got from it
AICAR and GW1516
Who has used this
Ok so buddy has given me a bottle of what appear to be a miracle drug and although I can find this profile, I can find any first hand experience with this drug, if you have used would you share your experience ? Thank you
AICAR and GW1516 experiments suggest that these two drugs, also called exercise in a pill, might protect against gaining weight on a high-fat diet, which might make it useful for treating obesity.
Researchers have identified two drugs, AICAR and GW1516, that mimic many of the physiological effects of exercise. The drugs increase the ability of cells to burn fat and are the first compounds that have been shown to enhance exercise endurance.
Both AICAR and GW1516 can be given orally and work by genetically reprogramming muscle fibers so they use energy better and contract repeatedly without fatigue. In laboratory experiments, mice taking the drugs ran faster and longer than normal mice on treadmill tests. Animals that were given AICAR, one of the two drugs, ran 44 percent longer than untreated animals. The second compound, GW1516, had a more dramatic impact on endurance, but only when combined with exercise.
Ronald M. Evans, the Howard Hughes Medical Institute investigator who led the study, said drugs that mimic exercise could offer potent protection against obesity and related metabolic disorders. They could also help counter the effects of devastating muscle-wasting diseases like muscular dystrophy. Evans and his colleagues, who are at the Salk Institute for Biological Studies, published their findings on July 31, 2008, in an advance online publication in the journal Cell.
Concerned about the potential for abuse of the two performance-enhancing drugs AICAR and GW1516, Evans has also developed a test to detect the substances in the blood and urine of athletes who may be looking for way to gain an edge on the competition.
In 2004, Evans and his colleagues genetically engineered mice that had altered muscle composition and enough physical endurance to run twice as far as normal mice. These “marathon mice” had an innate resistance to weight gain, even when fed a high-fat diet. “We made these mice and they had low blood sugar, they resisted weight gain, they had low fats in their blood. They were much healthier animals,” Evans said. “And when we put them on a treadmill, the engineered mice ran twice as far than normal mice - they transformed into remarkable runners.”
The scientists achieved these effects by modifying a gene called PPAR-delta, a master regulator of numerous genes. Evans and his colleagues showed that by enhancing PPAR-delta's activity, they had shifted the genetic network in muscle cells to favor burning fat over sugar as their energy source. But the effects seen in the marathon mice were caused by a genetic manipulation that was present in their bodies as their muscles were developing. Evans's group began to wonder whether they could duplicate these effects by turning on PPAR-delta in adult mice.
“We had shown that we could pre-program muscle using genetic engineering. If you express this gene while the muscle is being formed, you can increase the amount of non-fatiguing muscle fibers,” Evans says. “But what about reprogramming in an adult? When all the muscles are in place, can you give a drug that washes over the muscle for a few hours at a time and reprograms existing muscle fibers? That's a very different question.”
PPAR-delta has long been an attractive drug target because of its central role in metabolism, so Evans and his colleagues had no shortage of chemical compounds available to test. They began by testing a compound called GW1516. They treated young adult mice with the drug for five weeks. “We measured gene changes and the muscles looked like they were responding, so we knew the drug was working.”
Thus, while fully expecting the drug to dramatically increase endurance - Evans says, “There was no change at all in running performance. Nothing — not even a percent.”
Surprised by this spectacular failure, Evans and his colleagues decided to try a different approach, based on real-life experience. “If you're out of shape - and most of us are - and you want to change, you have to do some exercise. The way we reprogram muscle in adults is by training.”
So the scientists subjected two groups of mice — one that received the drug and one that did not — to interval training. The mice ran for 30 minutes on a slow treadmill five days a week for a total of four weeks. At the end of the training period, all of the mice - regardless of whether they had received GW1516 - had improved their performance. Those that had received GW1516, however, ran 68 percent longer than those that had only done the exercise training. “The dramatic effect of the drug was stunning,” Evans said.
The scientists were intrigued by this synergistic interaction and wanted to know how exercise allowed the drug to work. One possibility was an enzyme called AMP kinase (AMPK). During exercise, cells burn ATP as their primary source of energy. In the process, they create a by-product called AMP. When cells sense the presence of AMP, they activate AMPK. Activation of AMPK creates more ATP for the cell to burn. AMPK also triggers changes that lower blood sugar, sensitize cells to insulin, enable cells to burn more fat, suppress inflammation, and otherwise influence metabolic pathways. This is one reason that exercise is so beneficial.
Evans's team found that in addition to replenishing the cell's energy stores, AMPK also assists PPAR-delta in activating its gene targets. “It hops onto PPAR-delta in the nucleus and turbo-charges its transcriptional activity,” Evans explained. “We think AMPK activity is the secret to allowing PPAR-delta drugs to work.”
The critical question was whether chemical activation of AMPK is sufficient to trick the muscle into thinking it has been exercised. The second drug, called AICAR, enabled them to answer that question. AICAR mimics AMP, Evans said, “so muscle thinks it's burning fat.” The researchers were encouraged when they found that when they gave the drug to mice, they activated many of the genes in muscle that are turned on by exercise.
After four weeks of treatment with AICAR, Evans and his colleagues once again challenged sedentary mice to run on the treadmill. They found that mice that had received AICAR were able to run 44 percent longer than untreated mice. “This is a drug that is like pharmacological exercise,” Evans says. “After four weeks of receiving the drug, the mice were behaving as if they'd been exercised.” In fact, he says, those that got the drug actually ran longer and further than animals that received exercise training.
The animals receiving AICAR improved their running performance and their ability to burn fat. None of these effects, however, were as strong as they were in the animals that received both exercise and activation of PPAR-delta via GW1516.
Evans said this indicates that the benefits are likely due to collaboration between cells' AMPK and PPAR-delta signaling pathways. The team's genetic analyses supported this hypothesis; they found that AICAR and GW1516 alone activated a subset of exercise-induced genes, but activating both pathways (by combining GW1516 with exercise) activated a larger group of genes. Many of those genes regulate metabolism and muscle remodeling. Evans and his colleagues called this the “endurance gene signature.”
Like exercise, AICAR and GW1516 trigger a variety of changes that contribute to muscles cells' improved endurance and ability to burn fat. These changes include an increase in mitochondria, the structures responsible for producing energy; a shift in metabolism that takes advantage of lipids as an energy source; and an increase in blood flow, which enables the steady delivery of fat to burn. While the scientists only examined the drugs' effects on muscle cells in this study, Evans says it is likely that they confer benefits on other systems impacted by exercise, such as the heart and lungs.
Based on his group's findings, Evans is optimistic about using small molecules that mimic exercise to treat and prevent a variety of common conditions. For example, the way in which AICAR and GW1516 transformed the muscle fibers of mice suggests they might help reverse the muscle frailty associated with aging or diseases like muscular dystrophy. “We have now created the potential for a really simple intervention in an area of major health problems for which there is no intervention,” he says.
More broadly, AICAR and GW1516 could offer the benefits of exercise to people who do not get enough. “Almost no one gets the recommended 40 minutes to an hour per day of exercise,” he says. “For this group of people, if there was a way to mimic exercise, it would make the quality of exercise that they do much more efficient. This might be enough to move people out of the `danger zone' toward a lower risk, healthier set point. By intervening early, you may forestall the emergence of more serious problems.”
Evans expects these types of drugs will be attractive to a variety of individuals. “If you like exercise, you like the idea of getting more bang for your buck,” he says of GW1516. “If you don't like exercise, you love the idea of getting the benefits from a pill,” as with AICAR. So, while Evans sees tremendous opportunities for health benefits from drugs that mimic exercise, he also sees serious potential for abuse.
“Drugs that improve health are not only going to be used by people who have medical problems. They may also be used by people who are healthy - or by athletes who want an edge,” said Evans. He noted that the sports world has long been aware of his lab's work demonstrating a link between PPAR-delta and endurance. What's more, GW1516 has a relatively simple chemical structure and can be synthesized easily. Evans anticipates that athletes will seek their own sources of the drug - if they haven't already.
Concerned about the potential for abuse, Evans thought it was important to develop a test that could detect whether the drug was being used as a performance-enhancing substance. With HHMI support, his group has created a highly sensitive test that uses mass spectrometry to detect the two drugs and their metabolic by-products in the blood or urine. While the test is very reliable in mice, Evans says that further analyses are needed to ensure that it is accurate in humans. Evans, HHMI and the World Anti-Doping Agency are now working to certify the detection system and make it available in time to retroactively test athletes who compete in the 2008 Olympics Submitted by Armen Hareyan
developed by one of the largest drug companies in the world
i have the GW1516
GW1516, also written GW 50516, is a drug and research chemical developed by pharmaceutical client GlaxoSmithKline, which acts as a PPARδ (peroxisome proliferator activated receptor delta) modulator and selective agonist. GW1516 activates AMP-K (5' adenosine monophosphate-activated protein kinase) and stimulates skeletal muscle glucose uptake.
GW1516 has been demonstrated to effectively reverse metabolic abnormalities in obese men with metabolic syndrome (a pre-diabetic condition), likely due to the fact that it stimulus fatty acid oxidation.
GW1516 holds promise for treating obesity and adiposity and has been touted, much like AICAR, as "exercise in a pill," etc. In conjunction with AICAR, an AMPK agonist which acts synergistically with GW1516, significant increases in exercise endurance have been demonstrated in animal studies.
Ali et al write on the role of PPARk in the body's normal functioning:
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcriptional regulators. PPARdelta has an established role in metabolism, wound healing, and angiogenesis. However, little is known about its function in endothelial homeostasis. 
Ali et also infer from their data that PPARk agonists may be a hopeful area of study for treating vascular issues or perhaps preventing vascular issues by promoting stress resistance:
We have identified an important relationship between PPARdelta, PGC1alpha, and haem oxygenase-1, demonstrating that haem oxygenase-1 induction plays an important role in cytoprotective actions of PPARdelta ligands in vascular endothelium. In light of the protective effects of haem oxygenase-1 against atherogenesis, we suggest that PPARdelta represents a potentially important therapeutic target in the vasculature.
Foreman et al conclude that "proliferation of the C20 mouse mammary gland cancer cell line is inhibited by ligand activation of PPARbeta/delta due in part to increased apoptosis" meaning that as an additive therapy, PPARdelta agonists such as GW1516 may be useful for treating certain types of cancer or for promoting continued remission.
Dimoupolos et al write:
Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.
Wang et al show that PPARdelta agonists are useful targets for investigation regarding obesity prevention:
[T]argeted activation of PPARdelta in adipose tissue specifically induces expression of genes required for fatty acid oxidation and energy dissipation, which in turn leads to improved lipid profiles and reduced adiposity. ...In vitro, activation of PPARdelta in adipocytes and skeletal muscle cells promotes fatty acid oxidation and utilization. Our findings suggest that PPARdelta serves as a widespread regulator of fat burning and identify PPARdelta as a potential target in treatment of obesity and its associated disorders.
Narkar et al, authors of the pioneering study on AICAR, highlight some of the reasons GW1516 and other "exercise mimetics" are desirable for treating conditions prevalent in the current medical milieu:
The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.
 Sznaidman ML, Haffner CD, Maloney PR, Fivush A, Chao E, Goreham D, Sierra ML, LeGrumelec C, Xu HE, Montana VG, Lambert MH, Willson TM, Oliver WR Jr, Sternbach DD (May 2003). "Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity". Bioorg. Med. Chem. Lett. 13 (9): 1517–21.
Dimopoulos N, Watson M, Green C, Hundal HS (October 2007). "The PPAR delta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilization or insulin sensitivity in rat L6 skeletal muscle cells". FEBS Lett. 581 (24): 4743–8.
Krämer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM, Krook A (July 2007). "Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle". J. Biol. Chem. 282 (27): 19313–20.
Risérus U, Sprecher D, Johnson T, Olson E, Hirschberg S, Liu A, Fang Z, Hegde P, Richards D, Sarov-Blat L, Strum JC, Basu S, Cheeseman J, Fielding BA, Humphreys SM, Danoff T, Moore NR, Murgatroyd P, O'Rahilly S, Sutton P, Willson T, Hassall D, Frayn KN, Karpe F (February 2008). "Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men". Diabetes 57 (2): 332–9.
Narkar VA, Downes M, Yu RT, Embler E, Wang Y-X, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ,2 Evans RM (August 2008). "AMPK and PPAR Agonists Are Exercise Mimetics". Cell 134: 1–11.
 "Exercise In A Pill: Researchers Identify Drugs That Enhance Exercise Endurance". Science News. ScienceDaily. 2008-08-01. (Science Daily)
Ali F, Ali NS, Bauer A, Boyle JJ, Hamdulay SS, Haskard DO, Randi AM, Mason JC. PPARdelta and PGC1alpha act cooperatively to induce haem oxygenase-1 and enhance vascular endothelial cell resistance to stress. Cardiovasc Res. 2010 Mar 1;85(4):701-10.
Foreman JE, Sharma AK, Amin S, Gonzalez FJ, Peters JM. Ligand activation of peroxisome proliferator-activated receptor-beta/delta
(PPARbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line. Cancer Lett. 2010 Feb 28;288(2):219-25.
 Dimopoulos N, Watson M, Green C, Hundal HS. The PPAR delta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilization or insulin sensitivity in rat L6 skeletal muscle cells. FEBS Lett. 2007 Oct 2;581(24):4743-8.
Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell. 2003 Apr 18;113(2):159-70.
 Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008 Aug 8;134(3):405-15.
Well i have found next to no user experience online however the friend who gave this to me got down to A RIPPED 5% and yes his diet and traing of course was on point but he knows his gears and is crediting this in large part
and just to be clear he is not selling this to me he is giving it to me and GlaxoSmithKline is no research UGL chemical company it is one of the largest drug companies in the world with revenues of $45.2 BILLION