Why a PPAR Agonist is Not a SARM?
The take home points:
- PPAR agonists possess no anabolic activity and do no bind to the androgen receptor.
- PPAR agonists do not suppress HPTA or effect testosterone production in any way.
- PPAR agonists increase endurance but carry no stimulant nature so they will not affect sleep or cortisol levels.
PPAR agonists act upon the peroxisome proliferator-activated receptor (PPAR). PPARs form heterodimers with Retinoid-X Receptors (RXRs). The PPAR/RXR dimer formed then binds to a peroxisome proliferators-response element. This binding stimulates the expression of genes involved in the metabolism of glucose and fatty acids.
There are three different PPAR isoforms:
- Alpha (a)
- gamma (?)
- beta/delta (ß/ d)
Why a PPAR Agonist is Not a SARM.
PPAR-alpha is found in all metabolically active tissues such as the liver, adipocytes (fat cells), and skeletal muscle. It is involved in lipid metabolism and regulation of macrophages.
Macrophages are cells that are responsible for the elimination of disease-causing germs, dead cells and cellular debris.
Activation of PPAR-alpha increases the expression of lipoprotein lipase and apolipoprotein A-V and decreases the expression of apoC-III in the liver. This decreases LDL levels, decreases blood triglycerides levels and liberates fatty acids, allowing them to be burned.
LDL stands for low density lipoprotein and is often referred to as bad cholesterol. A lipase is an enzyme that helps break down fatty acids into glycerol and fatty acids.
In addition, PPAR-alpha activation increases hepatic apoA-I andapoA-II, which increasing HDL levels.
Side Note: HDL stands for high density lipoprotein and if often referred to as good cholesterol.
PPAR-alpha activation increases fat loss and improves cholesterol levels by lowering LDL levels, lowering blood triglycerides and increasing HDL levels.
PPAR-gamma is found primarily in fat cells, endothelium, smooth muscle, and macrophages. It is involved in the storage of fatty acids and is activated by leukotrienes, prostaglandins, and fatty acids.
Leukotrienes are a group of compounds derived from arachidonic acid that participate in inflammatory reactions. Prostaglandins regulate blood pressure, smooth muscle activity, inflammation, calcium movement, hormone regulation, and cell growth.
Activation of PPAR-gamma increases the transcription of genes and enzymes involved in insulin sensitivity and decreases their activity in adipogenesis (fat cell creation) and the inflammatory process.
Obesity and insulin resistance suppress PPAR-gamma activation. Activation of PPAR-gamma could theoretically cure type 2 diabetes. In fact, the anti-diabetic drug thiazolidinediones has been successfully used to treat type-2 diabetes in human clinical trials through its role in activating PPAR-gamma. However, hepatoxicity and risk of congestive heart failure discontinued the research on the drug.
The exact actions of PPAR-beta/delta in humans are still being researched. Animal studies show that PPAR-beta/delta activation decreases adiposity tissue (body fat). Most researchers speculate that PPAR-beta/delta acts similarly to PPAR-alpha but with more specific actions in skeletal muscle.
Cardarine (GW501516) is a PPAR receptor agonist developed by Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s. Cardarine was created to treat obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases. Those who run blood work when using cardarine will notice that their cholesterol levels improve substantially.
In 2007 research was published showing that mice given GW501516 had dramatically improved physical performance. This instantly popularized the drug as a doping agent. The World Anti-Doping Agency (WADA) added cardarine to the prohibited list in 2009.
Since cardarine is non hormonal, there is no need to worry about PCT or hormone suppression. The recommended dose for both men and women are 10-20 milligrams (mg) per day. The half-life of cardarine is 20-24 hours, meaning that a once per day dose is all that is needed.
Selective Androgen Receptor Modulators (SARMs) are a class of hormones that have similar properties to steroids, but with reduced androgenic properties and much more selective mechanisms of action. SARMS have a special affinity for certain tissues like muscle and bone, but not for other tissues like the prostate, liver, and brain.
SARMS don’t convert into unwanted molecules like estrogen, prolactin or DHT. This makes side effects associated with steroid usage like gynecomastia, water retention, hair loss etc. impossible with SARM usage.
There is a misconception floating around that SARMS are completely anabolic substances and carry no androgenic properties. This is not technically true as SARMS do have a high binding affinity for the androgen receptor and possess some androgenic properties.
However, the androgenic properties of SARMS are so minimal that they are pretty much negligible. Even RAD140, the most androgenic SARM, has only one tenth the androgenic properties of testosterone.
SARMs will suppress natural testosterone production and HPTA function but their rate of suppression is minimal and nowhere near the rate of suppression of anabolic steroids. Although SARMS are only minimally suppressive, it is still important to run a post cycle therapy (PCT) after each cycle.