GW1515 is the BOMB!

[johnjuanb1]

Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells.
Coll T, et al. Endocrinology. 2010.

Abstract

Elevated plasma free fatty acids cause insulin resistance in skeletal muscle through the activation of a chronic inflammatory process. This process involves nuclear factor (NF)-kappaB activation as a result of diacylglycerol (DAG) accumulation and subsequent 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. These effects were abolished in the presence of the carnitine palmitoyltransferase-1 inhibitor etomoxir, thereby indicating that increased fatty acid oxidation was involved in the changes observed. Consistent with these findings, PPARdelta activation by GW501516 blocked palmitate-induced NF-kappaB DNA-binding activity. Likewise, drug treatment inhibited the increase in IL-6 expression caused by palmitate in C2C12 and human skeletal muscle cells as well as the protein secretion of this cytokine. 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. Our results point to PPARdelta activation as a pharmacological target to prevent insulin resistance.

 

[mikennrg]

What do you guys think about GW for fat loss?

Many say it does nothing but I definately noticed a difference when I did my 60day run. Maybe its time to run it again hmmm.....

Regardless of dose you have to do cardio to get enhanced fat burning. This doesn't work like a stimulant or dnp. I have a physical job and I see good fat burning on just 5mg.

 

[tjitsu]

Regardless of dose you have to do cardio to get enhanced fat burning. This doesn't work like a stimulant or dnp. I have a physical job and I see good fat burning on just 5mg.

Agree 100% Im also on my feet allday 8h aday moving all the the time, my neat is through the roof already so I have no room for cardio or need, but my legs ache everyday also.

 

[Elvia1023]

I personally don't notice fat loss from it but that's solely due to my workout regimen. As mentioned above if you use the GW benefits for better cardio sessions it will only help you get leaner. My endurance goes up in the gym when lifting weight but I don't burn more calories on/off it as my workouts tend to be similar (common sense). I love the stuff though and anything that can boost HDL is good in my books. Next time I try and get ripped I will implement some cardio and GW and I know it will help give me that extra boost. I don't really like the traditonal fat burners (clen, eca, t3/t4) when cutting so go without most of them so GW is a great tool for me.

 

[johnjuanb1]

Are any of you guys stacking AICAR with GW-501516?

 

[johnjuanb1]

This GW-501516 is amazing!!!
My endurance is through the roof!
I did a full chest workout consisting of 5 exercises 20 sets total. Then i did a full arm workout consisting of 3 triceps exercises and 3 biceps exercises, 24 total sets and some were giant sets. I couldn’t rest. I had to superset everything for arms because resting was driving me crazy!!!
So i see why GW-501516 burns fat, because you can train forever!!!
Bear in mind my endurance is usually terrible!

 

[johnjuanb1]

GW-501516, also known as Cardarine, is a PPAR agonist that has been shown to have positive effects on muscle building, endurance, increased HDL (good) and decreased LDL (bad) cholesterol, and body recomposition. Cardarine currently has no human studies, but rodent studies have been very encouraging.

When combined with exercise, GW-501516 combined with four weeks of running increased running time by 68%; running distance by 70%; and doubled overall muscular endurance0. Along with exercise, GW-501516 increased mitochondrial growth by 50%. Additionally, GW-501516 on its own has been found to activate many of the genes that activate when an organism goes for a run or exercises.

I can definitely use the help with elevating my HDL.

 

[johnjuanb1]

I just took my 10mg GW-501516 for Day #3.
Today is leg day.

 

[johnjuanb1]

I really like this GW-501516!!!
I just finished legs. Yesterday i skipped the gym. The leg workout felt real good. I started 10mg GW-501516 four days ago and my endurance is so much higher. I don’t get winded like i usually do.
I did:
5 sets single legged leg press horizontal
4 sets seated leg curl
4 sets leg extensions
4 sets horizontal leg press both legs
6 sets seated calve raises

 

[sodzl]

Anyone have experience with raw gw5156 powder?

 

[intensed]

Does this study relate?

GW501516 (also known as GW-501,516, GW1516, GSK-516 and on the black market as Endurobol[1]) is a PPARδ receptor agonist that was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s, was entered into clinical development as a drug candidate for metabolic diseases and cardiovascular diseases, and was abandoned in 2007 because animal testing showed that the drug caused cancer to develop rapidly in several organs.[2]

 

[johnjuanb1]

GW501516 (also known as GW-501,516, GW1516, GSK-516 and on the black market as Endurobol[1]) is a PPARδ receptor agonist that was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s, was entered into clinical development as a drug candidate for metabolic diseases and cardiovascular diseases, and was abandoned in 2007 because animal testing showed that the drug caused cancer to develop rapidly in several organs.[2]

It was proven to be bs. The dose equivalent in humans would be ridiculous!
In fact more current research shows GW-501516 kills cancer cells. I’ll post a couple abstracts showing GW-501516 as promising in killing two types of cancer.

 

[johnjuanb1]

Apoptotic effect of the selective PPARβ/δ agonist GW501516 in invasive bladder cancer cells.
Péchery A, et al. Tumour Biol. 2016.
[/b]
Abstract

GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). This molecule promoted the inhibition of proliferation and apoptosis in few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARβ/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARβ/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.

 

[johnjuanb1]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614479/#ab0010title

Therapeutic potential of GW501516 and the role of Peroxisome proliferator-activated receptor β/δ and B-cell lymphoma 6 in inflammatory signaling in human pancreatic cancer cells

Abstract

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a member of the nuclear receptor superfamily and a ligand-activated transcription factor that is involved in the regulation of the inflammatory response via activation of anti-inflammatory target genes and ligand-induced disassociation with the transcriptional repressor B-cell lymphoma 6 (BCL6). Chronic pancreatitis is considered to be a significant etiological factor for pancreatic cancer development, and a better understanding of the underlying mechanisms of the transition between inflammation and carcinogenesis would help further elucidate chemopreventative options. The aim of this study was to determine the role of PPARβ/δ and BCL6 in human pancreatic cancer of ductal origin, as well as the therapeutic potential of PPARβ/δ agonist, GW501516. Over-expression of PPARβ/δ inhibited basal and TNFα-induced Nfkb luciferase activity. GW501516-activated PPARβ/δ suppressed TNFα-induced Nfkb reporter activity. RNAi knockdown of Pparb attenuated the GW501516 effect on Nfkb luciferase, while knockdown of Bcl6 enhanced TNFα-induced Nfkb activity. PPARβ/δ activation induced expression of several anti-inflammatory genes in a dose-dependent manner, and GW501516 inhibited Mcp1 promoter-driven luciferase in a BCL6-dependent manner. Several pro-inflammatory genes were suppressed in a BCL6-dependent manner. Conditioned media from GW501516-treated pancreatic cancer cells suppressed pro-inflammatory expression in THP-1 macrophages as well as reduced invasiveness across a basement membrane. These results demonstrate that PPARβ/δ and BCL6 regulate anti-inflammatory signaling in human pancreatic cancer cells by inhibiting NFκB and pro-inflammatory gene expression, and via induction of anti-inflammatory target genes. Activation of PPARβ/δ may be a useful target in pancreatic cancer therapeutics.

 

[johnjuanb1]

I see new veins coming out in my delts. I actually lowered my T4 too. I think it’s from the GW-501516. I lowered carbs a bit. I’m not quite ready to go into full on cutting for summer yet. I’m thinking about it but i love bread.

 

[johnjuanb1]

Time to take my 10mg GW-501516. Today I’m going to try two workouts in one because I’ve missed workouts due to work. Let’s see how my endurance is.

 

[Bio]

I need this! Chronic pain has me tired all the time..

 

[johnjuanb1]

I need this! Chronic pain has me tired all the time..

That would wear you down for sure being in pain all the time.
Mike Arnold’s Vicaine helps with pain and energy. The flmodanifil has a 14 hour half life so it’s a great pick me up. The tianeptine helps with pain.
With GW-501516 i feel the endurance increase while training but my energy feels normal at work. Once i start working out i can train forever.

 

[johnjuanb1]

I lifted weights twice today. GW is definitely amazing for muscular endurance.

 

[johnjuanb1]

I really like this GW-501516. I never eat fast food or cheat food, but i haven’t cut out bread yet. My food meals are typically turkey breast, egg whites, and rice but i also have 1,000 calories per day from bagels and sour dough bread. Hahaha so I’m not doing a true precontest diet obviously but I’m seeing more details since adding in the GW. I don’t do cardio but i did lift weights twice yesterday. I think on a true precontest diet you would really see real good fat loss from GW because you want to train more often and longer because your muscular endurance is higher. When i do a true precontest diet, most likely in June, I’d like to try GW-501516 and AICAR. My buddy said when he stacked both he saw very fast fat loss. I have yet to try AICAR myself.