GW501516 (also known as GW501, GW516, GW1516) belongs to family of drugs that act on the PPARD receptors and is an oral drug that is bioactive (has interaction with or effect on cell tissue) in humans.
PPARD is believed to work at the gene level and affects skeletal muscle metabolism. In one laboratory study, PPARD activation seemed to nearly double the Performance of running endurance in untrained adult mice.
Other potential functions of GW501516 include its regulation of fat metabolism, glucose uptake in skeletal muscle tissue and an increase in muscle gene expression.
The combined effects of these various functions suggest it has a role in burning fat for energy instead of carbohydrates or muscle protein.
As such, it fits within an area of research into clinical applications for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar.
In studies on mice, GW501516 led to increases in muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet.
Abstract: We evaluated the effects of GW501516, a specific peroxisome proliferator-activated receptor β/δ (PPARδ) agonist in metabolic syndrome mice, obtained by perinatal injection of monosodium l-glutamate, to investigate the efficacy of GW501516 against metabolic syndrome and the effectiveness of PPARδ activation as therapeutic target for metabolic syndrome. After 14 days treatment, GW501516 effectively improved the glucose intolerance, normalized the fasted blood glucose, and increased the serum high-density lipoprotein cholesterol (HDL-C) level. Postprandial blood glucose, serum insulin, leptin, free fatty acid (FFA) levels, and total cholesterol/HDL-C ratio were also significantly decreased. Moreover, semiquantitative reverse transcriptionpolymerase chain reaction results indicated that the above phenotypes might be due to (i) enhancement of fatty acid oxidation in muscle, adipose tissue and the liver; (ii) improvement of insulin-stimulated glucose transportation in skeletal muscle and adipose tissue; and (iii) reduced local glucocorticoid synthesis. Therefore, GW501516 could significantly ameliorate dyslipidaemia and insulin resistance in monosodium l-glutamate mice and activation of PPARδ could be envisioned as a useful strategy against human metabolic syndrome and related diseases.
GW-501516 helps repair the liver after injury...
GW501516-activated PPARβ/δ promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation
After liver injury, the repair process comprises activation and proliferation of hepatic stellate cells (HSCs), which produce extracellular matrix (ECM) proteins. Peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in these cells, but its function in liver repair remains incompletely understood. This study investigated whether activation of PPARβ/δ with the ligand GW501516 influenced the fibrotic response to injury from chronic carbon tetrachloride (CCl4) treatment in mice. Wild type and PPARβ/δ-null mice were treated with CCl4 alone or CCl4 co-administered with GW501516. To unveil mechanisms underlying the PPARβ/δ-dependent effects, we analyzed the proliferative response of human LX-2 HSCs to GW501516 in the presence or absence of PPARβ/δ.
We found that GW501516 treatment enhanced the fibrotic response. Compared to the other experimental groups, CCl4/GW501516-treated wild type mice exhibited increased expression of various profibrotic and pro-inflammatory genes, such as those involved in extracellular matrix deposition and macrophage recruitment. Importantly, compared to healthy liver, hepatic fibrotic tissues from alcoholic patients showed increased expression of several PPAR target genes, including phosphoinositide-dependent kinase-1, transforming growth factor beta-1, and monocyte chemoattractant protein-1. GW501516 stimulated HSC proliferation that caused enhanced fibrotic and inflammatory responses, by increasing the phosphorylation of p38 and c-Jun N-terminal kinases through the phosphoinositide-3 kinase/protein kinase-C alpha/beta mixed lineage kinase-3 pathway.
This study clarified the mechanism underlying GW501516-dependent promotion of hepatic repair by stimulating proliferation of HSCs via the p38 and JNK MAPK pathways.
Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.
Olson EJ1, Pearce GL, Jones NP, Sprecher DL.
Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins.
METHODS AND RESULTS:
GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL).
GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.
PMID: 22814748 [PubMed - indexed for MEDLINE]
Post from Evolutionary.org
Combating the cardiovascular side effects of trenbolone with GW-501516
As many of you know, Trenbolone is one of, if not THE strongest steroid that is available today. The drastic changes that occur with its usage are superman like to say the least. The problem with tren being as strong as it is comes in the form of the many negative side effects that it can produce. The list is long and extreme when it comes to side effects associated with tren usage. Here is list of possible and probably side effects: Increase in prolactin, acne, hair loss, insomnia, excess sweating, night sweats, rapid heart rate, anxiety, loss of libido and erectile disfunction, increase in blood pressure and cholesterol.
Another side effect that can deter a lot of people from its use is the horrible effect that it has on cardiovascular performance. Tren can drastically reduce your cardiovascular output and make any type of endurance activity much harder than it should be. Finally, there is an answer to combat this problem. By incorporating GW-510516 (Cardarine) you can counteract the negative cardiovascular effects from tren and allow yourself to perform cardiovascular exercises, both aerobic and anaerobic, as you normally would have. GW-501516 has been banned by the WADA (world anti doping association) because of the drastic advantage it gives athletes competing in endurance events. The amount of endurance it provides is extremely high and it allows you to maximize your efforts in everything that you are doing. By adding GW to your cycle, especially with tren, you will see that you can recover at much more rapid pace and you can go longer and harder with your workouts than you could have ever thought about doing before. Allowing yourself to maximize your cardiovascular output on tren will enhance the already drastic results it provides and allow a user to reach goals and peaks that were not though possible. Beyond the fact that your endurance and stamina will be increased, there are other benefits, especially to go along with tren sides, that GW will provide. GW has shown to increase good cholesterol and decrease bad cholesterol, through multiple studies, between 50-70%. To add to this, GW can have a VERY POSITIVE IMPACT ON BLOOD PRESSURE. By allowing you to increase your endurance in such a drastic way, GW-501516 allows for a major increase in cardiovascular health, allowing for optimal blood pressure and an overall much better state of health as well as sense of well being
The benefits of GW-501516 are very apparent and noteworthy. The fact that there is finally something that can be used safely with tren, and combat the cardiovascular side effects, as well as many others, is nothing short of amazing. This is a protocol that more and more people are beginning to use and will continue to use in the future. The optimal dosing of GW-501516 is 20 mg a day. You can run this up to 12 weeks at this dosage before needing a 4 week rest period. After your rest period, you can start running it again.