PPAR-delta, the New Potential Treatment for Metabolic Syndrome, May Be Produced by Your Own Body

Vincent C.W. Chen, PhD

Metabolic syndrome, a condition including insulin resistance (causing diabetes), obesity, hyperlipidemia (high blood lipids), hypertension (high blood pressure), and heart disease, is mainly due to unbalanced diets and lack of physical activity. It has become a major health concern in modern society. Recently, a substance called PPAR-delta has been identified as a potential therapeutic remedy for the treatment of metabolic syndrome.

PPAR-delta is the most abundant isoform among the three PPARs (peroxisome proliferator-activated receptors) in skeletal muscle. Skeletal muscle accounts for about 50% of whole body mass, and more than 50% of metabolism occurs in it. Therefore, activities involved in muscle contraction may significantly increase energy expenditure and result in the usage of glucose or breakdown of fat as fuel. PPAR-delta encourages skeletal muscle to burn stored fat as fuel. It can be greatly beneficial because it decreases triglyceride (a form of fat) and LDL-cholesterol (aka bad cholesterol) levels and increases insulin sensitivity and HDL-cholesterol (aka good cholesterol) levels. Since metabolic syndrome is a problem that may be avoided by decreasing body fat, PPAR-delta has been recognized to be a possible solution because it makes the body burn more fat.

Exercise has been emphasized for its multiple health benefits. Since exercise is associated with energy expenditure and PPAR-delta is associated with energy production, it is no surprise that our bodies can naturally produce more PPAR-delta in skeletal muscle simply by exercising. Research has shown that endurance (aerobic) exercise, such as running or jogging, may result in the increase of PPAR-delta levels in skeletal muscle. Fat is the main source of fuel for endurance exercise; therefore, PPAR-delta is produced to increase the breakdown of body fat to generate energy. Indeed, the increase of PPAR-delta helps you lose fat and exercise longer because it facilitates the use of fat.

On the other hand, resistance (anaerobic) exercise, such as weight lifting, was previously thought to be less related to fat metabolism and, therefore, less associated with PPAR-delta production. However, resistance exercise has been found to increase the ability of the body to utilize fat. Furthermore, PPAR-delta levels were found to rise following resistance exercise acutely and chronically in my recent studies. Resistance exercise uses glucose as the primary energy source, resulting in its depletion. The depletion of glucose stimulates PPAR-delta production to promote the use of fat in order to generate more energy. Therefore, resistance training not only increases muscle mass and strength but also has potential to prevent metabolic syndrome by increasing PPAR-delta production in skeletal muscle.

PPAR-delta is being developed to be a drug for the treatment of metabolic syndrome; however, our body can produce it simply by being active! Both endurance (aerobic) and resistance (anaerobic) exercises are good for health and fitness. Therefore, pick whatever exercise fits your interests, keep active, eat balanced and live healthily.


REFERENCES
1. Chen VCW, Lee CW, Bui S, Lee TV, Fluckey JD, Riechman SE.(2014). Skeletal Muscle PPAR-delta increases with 10 Weeks of Resistance Training. FASEB J. 28:lb819.
2. Chen VCW, Lee CW, Lee TV, Bui S, Riechman SE.(2011). The Effect of Acute High-intensity Resistance Exercise and Dietary Cholesterol on PPARδ Protein Content in Skeletal Muscle. FASEB J. 25:lb598
3. Barish, G. D., Narkar, V. A., & Evans, R. M. (2006). PPARδ: a dagger in the heart of the metabolic syndrome. The Journal of Clinical Investigation, 116, 590-597.
4. Brunmair, B., Brunmair, K., Dörig, J., Szöcs, Z., Stadlbauer, K., Marian, V., et al. (2006). Activation of PPAR-δ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids. Diabetologia, 49, 2713–2722.
5. Reilly, S. M., & Lee, C.-H. (2008). PPARδ as a therapeutic target in metabolic disease. Federation of European Biochemical Societies , 582, 26-31.


This article was originally published in the Sydney & J.L. Huffines Institute for Sports Medicine & Human Performance website (2011)

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