GW-501515 Reduces Cardiac Inflammation

[johnjuanb1]

GW-501515 Reduces inflammation in cardiac muscle.
PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells.

AuthorsAlvarez-Guardia D, et al. Show all Journal
Biochim Biophys Acta. 2011 Feb;1811(2):59-67. doi: 10.1016/j.bbalip.2010.11.002. Epub 2010 Nov 9.

Affiliation
Abstract
Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state.

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[johnjuanb1]

GW-501515 Reduces Systemic Inflammation

The PPARdelta agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition.

AuthorsKino T, et al. Show all Journal
Eur J Clin Invest. 2007 May;37(5):425-33.

Affiliation
Abstract
BACKGROUND: Interleukin-6 and downstream liver effectors acute phase reactants are implicated in the systemic inflammatory reaction. Peroxisome proliferator-activated receptor delta (PPARdelta), which binds to and is activated by a variety of fatty acids, was recently shown to have anti-inflammatory actions.

MATERIALS AND METHODS: We examined the ability of the synthetic PPARdelta agonist GW501516 to suppress interleukin-6-induced expression of acute phase proteins in human hepatoma HepG2 cells and rat primary hepatocytes. Results GW501516 dose-dependently suppressed interleukin-6-induced mRNA expression of the acute phase protein alpha1-antichymotrypsin in HepG2 cells. The compound also suppressed interleukin-6-induced mRNA expression of alpha2-acid glycoprotein, beta-fibrinogen and alpha2-macroglobulin in and the secretion of C-reactive protein by rat primary hepatocytes. Depletion of the PPARdelta receptor, but not of PPARalpha or gamma, attenuated the suppressive effect of GW501516 on interleukin-6-induced alpha1-antichymotrypsin mRNA expression, indicating that PPARdelta specifically mediated this effect. Since interleukin-6 stimulates the transcriptional activity of the alpha1-antichymotrypsin promoter by activating the signal transducer and activator of transcription (STAT) 3, we examined functional interaction of this transcription factor and PPARdelta on this promoter. Overexpression of PPARdelta enhanced the suppressive effect of GW501516 on STAT3-activated transcriptional activity of the alpha1-antichymotrypsin promoter, while GW501516 suppressed interleukin-6-induced binding of this transcription factor to this promoter.

CONCLUSIONS: These findings indicate that agonist-activated PPARdelta interferes with interleukin-6-induced acute phase reaction in the liver by inhibiting the transcriptional activity of STAT3. PPARdelta agonists might be useful for the suppression of systemic inflammatory reactions in which IL-6 plays a central role.


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[PEPTIDES-CHEMS]

Pretty good articles. :headbang:

.

 

[johnjuanb1]

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[Akamai]

But John those rats died of cancer. LOL

Ak

 

[johnjuanb1]

But John those rats died of cancer. LOL

Ak

Where does it say that it the study?

 

[johnjuanb1]

Akami....I found a recent study on GW-501516 that was published Nov. 01, 2013. It examines the conflicting studies with GW-501515 and it's benefits to risks ratio. Mega doses beyond anything a human would use led to cancer in rats. The same has been proven with nutrasweet. There are benefits to those with diabetes, fatty liver, inflammation in the body, that can benefit with GW. Not to mention the muscle building and fat loss properties. Anything in excess is carcinogenic realistically if it's stored in the body. I guess we leave it up to individual discretion to decide the fate of this research chem.

Harnessing the benefits of PPARβ/δ agonists.

AuthorsMackenzie LS, et al. Show all Journal
Life Sci. 2013 Dec 18;93(25-26):963-7. doi: 10.1016/j.lfs.2013.10.022. Epub 2013 Nov 1.

Affiliation
Abstract
Lipid mediators have complex effects on the cell; one of the key transcriptional factors that moderate proliferation and inflammatory effects is PPARβ/δ. Following highly successful clinical trials using the PPARβ/δ agonists GW501516 for treatment of diabetes, GSK announced that any further research would be discontinued due to preclinical trials in rodents which linked this drug to wide spread tumour development. In this review we outline the dual molecular functions of PPARβ/δ and connect these to the diverse results from in vitro studies, and draw parallels with the outcomes of animal and human studies. The PPARβ/δ agonists have a great potential in terms of therapy, and we hope to provide some insight into the reasons why such contrasting results have been published. The discussion presented here is important to the future development of PPARβ/δ agonists for the clinic, and for a fuller understanding for their complex regulatory roles in the cell.

 

[Akamai]

I was joking JJ. I don't put much credence in those mice cancer studies and how it translates to humans.

Ak

 

[johnjuanb1]

I was joking JJ. I don't put much credence in those mice cancer studies and how it translates to humans.

Ak

Yeah. I guess there's risk in using anything these days. Hahaha... a little slow sometimes. Getting old!

 

[cauthen96]

Good info as always JJ... Have you used gw personally and if so what protocol did you use?

 

[johnjuanb1]

Good info as always JJ... Have you used gw personally and if so what protocol did you use?

Yes. I ran it in mega doses as an experiment. I made a thread on it. It uses body fat for energy instead of carbohydrates. I would use it in lower doses next time as it felt similar to dnp at high doses but it burns fat real well. It also raises HDL in low doses I believe. I can't remember my dosing protocol off hand.

 

[johnjuanb1]

ENDURANCE and FAT LOSS

GW501516 (GW1516 or GSK-516) is a drug that acts as a PPARδ modulator. GW 501516 activates AMP-activated protein kinase and stimulates glucose uptake in skeletal muscle tissue, and GW 501516 has been demonstrated to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation. It has been proposed as a potential treatment for obesity and related conditions, especially when used in conjunction with a synergistic compound AICAR, as the combination has been shown to significantly increase exercise endurance in animal studies.

How it works:

GW501516 is a selective agonist (activator) of the PPARδ receptor. It displays high affinity (Ki = 1 nM) and potency (EC50 = 1 nM) for PPARδ with > 1000 fold selectivity over PPARα and PPARγ.

In rats, binding of GW501516 to PPARδ recruits the co activator PGC-1a. The PPARδ/coactivator complex in turn up regulates the expression of proteins involved in energy expenditure. Furthermore in rats treated with GW501516, increased fatty acid metabolism in skeletal muscle and protection against diet-induced obesity and type II diabetes was observed. In obese rhesus monkeys, GW501516 increased high-density lipoprotein (HDL) and lowered very-low-density lipoprotein (VLDL). The mechanism by which PPARδ agonists increase HDL appears to be a result of increased expression of the cholesterol transporter ABCA1.

Uses:

There are two main uses with GW-501516. The first and most common use is that of increased endurance. GW has been banned for professional athletes due to the unfair advantage it provides to endurance athletes. Anyone want a drastic increase in endurance will find that GW truly shines in this aspect. It takes effect very quickly and the results can be staggering. A common dose of 10 mg day will provide a significant increase in endurance.

The second common usage with GW is that of fat loss. Many users turn to GW as it has shown to melt off fat while still being non-catabolic. You will find that you can still hold on to some muscle as you are losing fat. It helps when you are running it in conjunction with SARMS Ostarine and S4, to hold on to as much muscle as possible. A dosage of 10 mg a day will provide good amounts of fat loss, but an increase to 20 mg a day will provide much more in this area.

GW 501516 can be ran in 8 week cycles, but as with any other steroid or supplement, it should be cycled properly to avoid any possible side effects and the keep it as effective as possible.

 

[Bionic]

It makes you wonder if it's so awesome and has so much potential, why would GSK drop it?

 

[yatyas314]

It makes you wonder if it's so awesome and has so much potential, why would GSK drop it?

Because it replaces like 4 drugs that they have patents on .

 

[Bionic]

Source?

 

[johnjuanb1]

It's works best at 10mg per day.

 

[Google&Pubmed]

Even at 5mg I was seeing amazing results. I had a eventing heart rate of 58 and when I did do cardio I had to bust my ass to get between 120-130. Its an amazing product but I do wonder like Bionic why GSK dropped it.

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[ironceltic12]

Even at 5mg I was seeing amazing results. I had a eventing heart rate of 58 and when I did do cardio I had to bust my ass to get between 120-130. Its an amazing product but I do wonder like Bionic why GSK dropped it.

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5mg once per day? Any specific protocol for this stuff? Is it best taken alone? Sorry I'm new to peptides and trying to learn a bit haha

 

[Google&Pubmed]

5mg once per day? Any specific protocol for this stuff? Is it best taken alone? Sorry I'm new to peptides and trying to learn a bit haha

No protocol. Literally I would wake up and just take 5mg and then couple of minutes later I would brush my teeth and go on with my day.


BTW I meant resting not "eventing".

 

[johnjuanb1]

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