PPARgamma agonist pioglitazone does not enhance performance in mice

Area of Science:

• Exercise Physiology
• Molecular Biology
• Pharmacology

Background:

• Peroxisome-proliferator-activated receptors (PPARs) and AMP-activated protein kinases (AMPKs) are key regulators of muscle metabolism and function.
• PPAR agonists like GW1516 and AMPK activators like AICAR are known performance enhancers, leading to their inclusion on WADA's prohibited list.
• Thiazolidinediones, such as pioglitazone, are PPARgamma agonists with potential to elicit biological effects similar to PPARdelta and PPARdelta-AMPK agonists.

Purpose of the Study:

• To investigate the effects of pioglitazone on mitochondrial biogenesis and exercise performance.
• To determine if pioglitazone influences key proteins and enzyme activity in the mitochondrial biogenesis pathway.
• To assess the impact of pioglitazone on maximal aerobic velocity, endurance capacity, and grip strength in trained animals.

Main Methods:

• Mice were subjected to a training regimen, with some receiving pioglitazone treatment.
• Blood glucose levels, protein expression of mitochondrial biogenesis intermediates (e.g., PGC-1α, NRF-1), and citrate synthase activity were measured in gastrocnemius and soleus muscles.
• Maximal aerobic velocity, endurance capacity, and grip strength were evaluated before and after the training period.

Main Results:

• Training significantly increased maximal aerobic velocity, endurance capacity, and grip strength.
• Soleus muscle showed significant increases in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor-1 (NRF-1) protein content, and citrate synthase activity following training.
• Pioglitazone administration did not significantly alter blood glucose levels, protein expression, or citrate synthase activity, indicating no treatment effect on the mitochondrial biogenesis pathway.

Conclusions:

• Exercise training effectively enhances mitochondrial biogenesis and improves physical performance in mice.
• Pioglitazone treatment, despite being a PPARgamma agonist, did not provide additional benefits to mitochondrial biogenesis signaling or performance beyond those achieved through training.
• The findings suggest that pioglitazone is not an effective modulator of mitochondrial biogenesis or exercise performance in this context.