Regular physical activity is crucial for maintaining a healthy weight, but some individuals may lose more weight than others through exercise. Researchers from Kobe University in Japan suggest that individuals who lose weight at a slower pace during regular physical activity might be lacking variants of the protein PGC-1α, which assists in regulating the body’s metabolism and response to short-term exercise. Their findings, published in the journal Molecular Metabolism, could pave the way for a new class of weight loss medications. PGC-1α is responsible for inducing gene expression related to mitochondria, fatty acid oxidation, and thermogenesis, promoting efficient energy consumption in muscles. The protein increases in skeletal muscle during exercise, leading to the enhancement of genes that facilitate energy expenditure.
Through their study utilizing both mouse and human models, researchers found that the absence of “b” and “c” versions of PGC-1α protein resulted in less fat burn during and after exercise. Individuals lacking these variants showed no impact from short-term physical activity, consuming less oxygen and having a higher percentage of body fat compared to those with the complete protein. Furthermore, mice lacking only PGC-1α b/c experienced reduced energy expenditure during exercise and gained weight despite normal food intake. This unique model highlighted the importance of energy expenditure efficiency in determining weight gain tendencies.
The development of weight loss medications, such as glucagon-like peptide-1 (GLP-1) receptor agonists, has gained popularity recently for their ability to suppress appetite and aid in weight loss. However, the discovery of PGC-1α b/c variants could lead to a new class of medications that promote weight loss regardless of diet. Rather than reducing food intake, these potential drugs would mimic the effects of exercise, offering a different approach to treating obesity. Understanding the mechanisms behind weight loss through exercise could also lead to improved exercise therapies and the development of drugs that replicate exercise effects.
Moving forward, researchers are investigating why the increase in PGC-1α b/c levels varies among individuals, potentially uncovering DNA methylation as a contributing factor. Additionally, they have identified a substance that has the potential to elevate PGC-1α b/c levels, suggesting the possibility of new anti-obesity drugs. Bariatric surgeon Mir Ali, MD, finds the study intriguing, noting the genetic component to exercise and weight loss. While exercise plays a role in weight management, Ali emphasizes that diet is the most significant factor in achieving weight loss results. Although exercise offers multiple health benefits, including cardiovascular health, the key to weight loss lies in a balanced and healthy diet.
