Grant: Discovery Grants Program - Individual

Being the largest tissue in mammals, skeletal muscle is an important consumer of energy. When muscle energy use is altered, it disrupts energy balance throughout the body. The long-term aim of my research is to better understand how muscle energy metabolism is regulated. For the next 5 years, my team will focus on how bisphenols (BPs) and myokines regulate muscle metabolism. BPs are used in the production of plastics. BPs have been shown to affect metabolism in mammals, but little is known regarding their effect on muscle. Our work shows that BPA, the most widely used BPs, increases the use of sugar by muscle, while decreasing the production of energy by mitochondria, the powerhouse of the cells. The plastics industry is now replacing BPA with analogues, but the effects of these analogues on muscle metabolism are unknown. Myokines are factors released by contracting muscle cells. It is believed that they improve the use of energy by muscle. However, too often, this effect has been shown using levels of myokines that cannot be reached in real life. We propose to use an isolated model of muscle cell contraction which is considered a better physiological model to study how all the myokines released during contraction improve muscle metabolism. Physical exercise was shown to reverse the negative effects of certain chemicals. However, if physical exercise, through the release of myokines, can counteract the effect of BPs on muscle metabolism is unknown. We propose to pursue the following short-term objectives: 1.To determine by which mechanisms BPs alter muscle metabolism and the communication between muscle and fat cells We will study the mechanisms involved in the effects of BPs on the use of sugar and the function of mitochondria using muscle cell models. We will also study how BPs alter the release of fat cell factors (adipokines), and how this modifies muscle cell metabolism. 2.To better understand the role of myokines in the metabolic adaptations of muscle during contraction Using a model of contracting muscle cells, we will study the molecular mechanisms by which physiological levels of myokines regulate muscle cell metabolism. 3.To determine if physical exercise and myokines can reverse the effects of BPA on muscle metabolism Using mice treated with environmental levels of BPA, we will determine if exercise protects against the effects of BPA on muscle metabolism. Our model of muscle contraction will allow us to determine if myokines are involved in this process. Our research should determine if BP-containing plastics disrupts muscle metabolism in mammals. It will also enable us to define the role myokines may play in the adaptation of muscle metabolism in response to muscle contraction. Ultimately, our research could strengthen the arguments of the Canadian government in support of their goal of zero plastic waste by 2030, but also contribute to better understand how being physically active is beneficial for muscle physiology.