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ScienceDaily_2013 12484.txt

#Differences between marathon mice and couch potato mice reveal key to muscle fitnessresearchers discovered that small pieces of genetic material called micrornas link the two defining characteristics of fit muscles: the ability to burn sugar and fat and the ability to switch between slow-and fast-twitch muscle fibers. The team used two complementary mouse models--the marathon mouse and the couch potato mouse--to make this discovery. But what's more they also found that active people have higher levels of one of these micrornas than sedentary people. These findings published May 8 in The Journal of Clinical Investigation suggest micrornas could be targeted for the development of new medical interventions aimed at improving muscle fitness in people with chronic illness or injury. In this study we wanted to determine on a molecular level what makes a muscle fit during development or following exercise. This information is relevant to our efforts to improve muscle fitness in many health conditions such as aging cancer and heart failure. These findings may also prove useful for our active members of the military who become'detrained'during injury and recovery time said Daniel P. Kelly M d. director of Sanford-Burnham's Diabetes and Obesity Research center and senior author of the study. Marathon vs. couch potato micefit muscle is known for its ability to do two things: 1) burn fat and sugars and2) switch between slow-twitch and fast-twitch muscles. According to Kelly muscle fitness only occurs if both are functioning properly. Increased muscle endurance cannot occur without boosting both of these muscle components. Kelly and his team set out to determine what connects muscle metabolism and structure. To do this they turned to two different mouse models each specially engineered to produce distinct but related proteins that turn muscle-specific genes on and off. The first model dubbed the marathon mouse has a muscle-gene regulator called PPARÎ/Î'.These mice can run much further than normal mice. The second model known as the couch potato mouse produces a different muscle-gene regulator called PPARÎ. These mice are able to burn a lot of fuel but they can't run very far. Micrornas in muscle fitnessto identify the link between muscle metabolism and muscle fiber type-switching Kelly's team compared the molecular differences between these two disparate mouse models. First the team found that PPARÎ couch potato mice have the optimal metabolic switch but lack the muscle fiber switch. In contrast PPARÎ/Î'marathon mice have the whole package necessary for muscle fitness. The two mouse models also differed in molecular profiling according to this study. The team discovered that marathon mice produce certain micrornas that are capable of activating the fiber switch. By comparison this same circuitry is suppressed in couch potato mice. Digging a little deeper Kelly's team determined that PPARÎ/Î'is connected to micrornas via an intermediary called estrogen-related receptor (ERRÎ. This protein collaborates with PPARÎ/Î'to turn on micrornas. That's why marathon mice are fitter and have more type I muscle fibers than couch potato mice--their PPARÎ/Î 'and ERRÎ induce the right micrornas. Muscle-boosting potential for patientsto determine if their findings were relevant to human health Kelly and his team worked with Steven R. Smith M d. director of the Florida Hospital--Sanford-Burnham Translational Research Institute for Metabolism and Diabetes. From there the team obtained muscle tissue from sedentary people (those who don't exercise regularly) and active people in good shape. Sure enough ERRÎ and one of the micrornas elevated in PPARÎ/Î'marathon mice were increased also in active people but not the sedentary group. We're now conducting additional human studies to further investigate the ERRÎ-microrna circuit as a potential avenue for improving fitness in people with chronic illness or injury Kelly said. For example next we want to know what happens to this circuit during exercise and what effect it has on the cardiovascular system. Story Source: The above story is provided based on materials by Sanford-Burnham Medical Research Institute. The original article was written by Heather Buschman. Note: Materials may be edited for content and length. Journal Reference

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