More info I found for those wanting to know....
GW-501516 is a PPARδ modulator compound is currently 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 trialed as a potential treatment for a few conditions consisting mainly of obesity, diabetes, dyslipidemia and heart disease. GW-501516 has a synergistic effect when combined with the AMP-K agonist AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than 40%. And from My own experience yes it works my friends.
GW-50156 regulates fat burning through a number of different pathways which includes exercise mimetic effects. It increases glycogen retention in skeletal muscle tissue while increasing muscle gene expression. This shift changes the body’s metabolism to allow for more fat burning and for energy instead of carbohydrates or protein as the source of fuel. This is why the main reason why it’s being looked into as a treatment for diabetes. As it will not allow the patients to endure and overly catabolic state, thus allowing energy levels and health to be stable at all times. GW-501516 clearly demonstrates that it increases muscle mass while keeping glucose from touching the adipose tissue sort of like Need2Slin but need2slin does much more then just this. Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans. We dive into its attributes further later in the article But again let me speak from personal experience. I did a test with this drug and Winstrol. I know for my self when I take wonstrol it always kills my cholesterol levels. Last time I took it I ended up with an HDL of ten and a LDL over two hundred and it only took less then 2 weeks for this to happen. So knowing this I took wintrol for 4 weeks and also took GW-501516 along with it and I was amazed at the results. My cholesterol levels were BETTER at the end of the 4 week trial. So if cholesterol is of concern for you then you need to get some of this stuff my friend because trust me it works.
Concerns had been raised right before the 2008 Beijing Olympics that GW-501516 could be used by athletes as a performance enhancing drug which was not detectable nor tested for during the doping test. The main reason why athletes would use it is because of the increase in endurance through the increase of glycogen storage leading to increased muscular endurance, again ring a bell. Need2Slin does THE SAME THING! GW-501516 has yet to be label a controlled or banned substance by any national drug enforcement agency including Wada. Obviously no one will test positive for this drug, so if I were an Olympic athlete looking for a boost; this would be at the top of the list considering its much outweighed pros over cons. Any Athletes looking for a edge can use this drug and never have to worry about popping hot. They can not test for it my friends so you are golden. Some new testing is coming out in the next 3-5 years that will allow them to basically test your DNA to see if your bosy as been drug altered in anyway but this is years in the making. For now you are safe to take GW-501516 and not have to worry about popping hot.
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. Researchers found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, they 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. Now how does this peptide cause mice to lose weight without activity? Simple, theActivation of PPARβ/δ by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, β-oxidation, cholesterol efflux, and energy uncoupling. In addition, the treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARβ/δ agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARγ induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyl-transferase-1 promoter is directly regulated by PPARβ/δ, and not PPARα in skeletal muscle cells in a PPARγ coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Overall the peptide GW501516 (PPARβ/δ agonists) would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARβ/δ may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity. (Dressel et al. 17 (12): 2477).. However I would advice only using this drug orally IMO..
Proof that GW5010516 increases insulin sensitivity Elevated plasma free fatty acids cause insulin resistance in skeletal muscle through the activation of a constant chronic inflammatory process. This process involves nuclear factor (NF)-kappaB activation as a result of diacylglycerol (DAG) accumulation and following protein kinase Ctheta (PKCtheta) phosphorylation. At present, it is unknown whether peroxisome proliferator-activated receptor-delta (PPARdelta) activation prevents fatty acid-induced inflammation and insulin resistance in skeletal muscle cells. In C2C12 skeletal muscle cells, the PPARdelta agonist GW501516 prevented phosphorylation of insulin receptor substrate-1 at Ser(307) and the inhibition of insulin-stimulated Akt phosphorylation caused by exposure to the saturated fatty acid palmitate. This latter effect was reversed by the PPARdelta antagonist GSK0660. Treatment with the PPARdelta agonist enhanced the expression of two well known PPARdelta target genes involved in fatty acid oxidation, carnitine palmitoyltransferase-1 and pyruvate dehydrogenase kinase 4 and increased the phosphorylation of AMP-activated protein kinase, preventing the reduction in fatty acid oxidation caused by palmitate exposure. In agreement with these changes, GW501516 treatment reversed the increase in DAG and PKCtheta activation caused by palmitate. Consistent with these findings, PPARdelta activation by GW501516 blocked palmitate-induced NF-kappaB DNA-binding activity. These findings indicate that PPARdelta attenuates fatty acid-induced NF-kappaB activation and the subsequent development of insulin resistance in skeletal muscle cells by reducing DAG accumulation. The results of the study clearly demonstrate that PPARdelta activation is a pharmacological target to prevent insulin resistance. (Endocrinology 2010 Apr; 151(4) :1560-9.)
The peroxisome proliferator-activated receptor δ (PPARδ) regulates the expression of genes involved in cellular lipid and cell energy metabolism in many metabolically active tissues, such as liver, muscle, and fat, and plays a role in the cellular response to stress and environmental stimuli. The particular role of PPARδ in insulin-secreting β-cells, however, is not well understood; we recently identified the cell-specific role of PPARδ on mitochondrial energy metabolism and insulin secretion in lipotoxic β-cells. After treatment of HIT-T15 cells, a syrian hamster pancreatic β-cell line, with high concentrations of palmitate and/or the specific PPARδ agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1α), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), the protein levels of the mitochondria uncoupling protein 2 (UCP2), mitochondrial morphology, the insulin secretion capacity and ATP/ADP ratio. Our results show that GW501516 treatment promoted generation of mitochondrial ATP, as well as expression levels of PGC-1α, NRF-1 and mtTFA, decreased basal insulin secretion, but had no effect on glucose-stimulated insulin secretion (GSIS), increased amounts of UCP2 and changed ATP-to-ADP ratio, improved mitochondrial morphology in palmitate-treated β-cells. GW501516-induced activation of PPARδ enhanced mitochondrial energy metabolism, but also promoted a concomitant mitochondrial uncoupling and resulted in decreased basal insulin secretion and restricted GSIS; this observation indicated the possible action of a protective mechanism responding to the alleviation of excessive lipid load and basal insulin secretion in lipotoxic β-cells. (Volume 343, Numbers 1-2, 249-256, DOI: 10.1007/s11010-010-0520-8) As you can see this peptide has a profound effect on the liver and pancreas resulting in lower blood sugar and controlled insulin output.
GW501516 prevents brain aging.
Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Peroxisome proliferator-associated receptor (PPAR) pathways are involved in the control of the inflammatory processes, and PPAR-β seems to play an important role in the regulation of central inflammation. In addition, PPAR-β agonists were shown to have trophic effects on oligodendrocytes in vitro, and to give partial protection in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516 is a specific PPAR-β agonist that researchers chose to examine for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-γ and LPS. GW 501516 decreased the IFN-γ-induced up-regulation of TNF-α and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-β agonist. However, it increased IL-6 m-RNA expression. In demyelinating cultures, reactivity of both microglial cells and astrocytes was observed, while the expression of the inflammatory cytokines and iNOS remained unaffected. Furthermore, GW 501516 did not protect against the demyelination-induced changes in gene expression. This suggests that the protective effects of PPAR-β agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes. We all know that both alzheimer’s and Dementia are caused by chronic inflammation within the brain. Further research is still needed but this peptide displays promise in preventing the aging of the brain. (Journal of Neuroinflammation 2009, 6:15 doi:10.1186/1742-2094-6-15)
GW501516 helps prevent the onset of Diabetes In contrast to the well-established roles of PPARgamma and PPARalpha in lipid metabolism, little is known for PPARdelta in this process. We show here that targeted 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. Importantly, these animals are completely resistant to both high-fat diet-induced and genetically predisposed (Lepr(db/db)) obesity. As predicted, acute treatment of Lepr(db/db) mice with a PPARdelta agonist depletes lipid accumulation. In parallel, PPARdelta-deficient mice challenged with high-fat diet show reduced energy uncoupling and are prone to obesity. 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. (Cell. 2003 Apr 18;113(2):159-70. PMID:12705865)
In vitro and in vivo genetic and pharmacological studies have demonstrated PPARα regulates lipid catabolism. In contrast, PPARγ regulates the conflicting process of lipid storage. However, relatively little is known about PPARβ/δ in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARα and -γ. PPARβ/δ, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Surprisingly, the role of PPARβ/δ in skeletal muscle has not been investigated. We utilize selective PPARα, -β/δ, -γ, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARβ/δ, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARβ/δ by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, β-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARβ/δ agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARγ induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyl-transferase-1 promoter is directly regulated by PPARβ/δ, and not PPARα in skeletal muscle cells in a PPARγ coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARβ/δ agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARβ/δ may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity. (Dressel et al. 17 (12): 2477)
GW5015016 decreases chances of Heart Disease The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes, respectively. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. These results suggest that PPARdelta agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease which is typically associated with the metabolic syndrome X. (Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11. Epub 2001 Apr 17. PMID:11309497)