Peroxisome proliferator-activated receptor delta (PPAR delta) is a naturally occurring protein. It functions like a cellular switch, controlling genes that guide how cells manage energy and perform their duties. Present across many tissues, it helps maintain biological balance and function.
The Biological Role of PPAR Delta
PPAR delta operates as a nuclear receptor within the cell’s nucleus. Its primary function is as a transcription factor, regulating specific gene expression. When a ligand molecule binds, the receptor changes, allowing it to bind to specific DNA sequences and influence which genes are turned on or off.
This protein is widely distributed, with high concentrations in metabolically active tissues like skeletal muscle, fat tissue, and the liver. Activated by natural molecules such as fatty acids, PPAR delta partners with retinoid X receptor (RXR).
This partnership, a heterodimer, then attaches to specific DNA segments called peroxisome proliferator response elements (PPREs). This binding initiates or represses target gene transcription, altering cellular processes to help cells adapt to their environment or energy needs.
Influence on Metabolism and Endurance
Activating PPAR delta significantly impacts the body’s metabolism and physical endurance. One main effect is promoting fatty acid oxidation, the process of burning fat for fuel. When activated, PPAR delta instructs muscle cells to shift their energy preference from glucose to fatty acids. This metabolic redirection provides a more sustained and efficient energy source, particularly during prolonged physical activity.
This metabolic shift to fat utilization directly contributes to increased physical endurance. By preserving glucose stores, the body can sustain activity longer, delaying fatigue. Studies show that activating PPAR delta enhances running endurance, partly by delaying low blood sugar levels.
PPAR delta also promotes mitochondrial biogenesis, the creation of new mitochondria. An increase in these organelles, which generate most cellular energy, means cells have a greater capacity for energy production, further supporting sustained physical performance.
Therapeutic and Performance-Enhancing Applications
Given its profound influence on metabolism, there has been considerable scientific interest in manipulating PPAR delta activity for therapeutic purposes. Researchers explored synthetic compounds, known as agonists, designed to activate the PPAR delta receptor. The goal was to develop treatments for metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia.
These agonists showed promise in preclinical animal studies by reducing weight gain, improving insulin sensitivity, and favorably affecting lipid profiles. For instance, the synthetic agonist GW501516, also known as Cardarine, reduced weight gain and lowered triglyceride levels in studies involving mice and obese monkeys. This led to its consideration as a potential drug.
However, the pursuit of these compounds extended beyond medical therapy into athletic performance enhancement. Cardarine became widely known for its illicit use by athletes and bodybuilders seeking a competitive edge, particularly in endurance sports, due to its purported ability to increase stamina and improve fat burning.
Health Risks and Controversies
Despite initial promise and adoption by some athletes, the clinical development of synthetic PPAR delta agonists like Cardarine was halted. This decision stemmed from serious safety concerns that emerged during preclinical animal trials. These studies revealed the compound caused cancer to develop rapidly and aggressively.
Long-term animal studies in mice and rats showed Cardarine promoted multiple types of cancer in various organs. The observed carcinogenic effects were severe enough for pharmaceutical companies to discontinue further human research, deeming the potential risks too substantial.
Consequently, Cardarine is not approved for human consumption by any regulatory agency worldwide. It is classified as a banned substance by organizations like the World Anti-Doping Agency (WADA) due to its performance-enhancing potential and associated health risks. Despite its unapproved status, Cardarine is still sold illegally on the black market, often with unknown purity, inconsistent dosages, and potential contamination, posing significant dangers to those who use it.