We all know that regular exercise is important to our health. But how does it affect patients with NAFL? Can we exercise the fat out of our liver? Are all types of training equally beneficial? I met with Professor Bente Klarlund Pedersen from Center for Physical Activity Research to hear her thoughts on the subject. Bente, why is exercise important for our health? Regular exercise decreases the risk of approximately 35 different diseases. That is type 2 diabetes, cardiovascular disease, dementia, and cancer. In fact, exercise decreases the risk of 13 different cancers. Exercise is also important for weight control. It lowers blood pressure, it lowers cholesterol, and it's good for our bones. So if you exercise, you have a decreased risk of osteoporosis. Then it's good for our mental health. It decreases the risk of stress, the psychological stress, and depression. You feel better, you feel more relaxed, and you sleep better. That's amazing. So exercise is clearly important for many things. What about the individuals with non-alcoholic fatty liver disease? Can exercise help these individuals as well? The answer is yes. We know that obesity and type 2 diabetes are strong risk factors for non-alcoholic fatty liver disease, and we know that exercise is important for weight control and that exercise enhances insulin sensitivity. Exercise is a very important lifestyle for people with NAFLD. Do you think that exercise affect NAFLD by body weight control, by losing body weight or is there an other mechanism? It's very interesting because we know from mice studies that if mice exercise, then it reduces the risk that obesity will lead to NAFLD. I'm personally convinced that exercise is good because you may lose weight, but it can also have a direct effect on NAFLD. I've been wondering, given your expertise in myokines, so the peptides and proteins secreted from the muscle under physical activity, could some of these myokines have an effect on NAFL, do you think? It's very likely, of course I have to speculate here, but we know that many of these myokines, these secreted products, these exercise factors, that they are involved in metabolism. So the myokines enhance insulin sensitivity, or the myokines enhance fat oxidation, and then there are a handful of myokines that are involved in mediating anti-inflammation, which could mean that exercise could also protect from NAFLD progressing to the inflammatory condition called NASH or non-alcoholic steatohepatitis. We agree that exercise can be beneficial for your liver. Is there are different sort of exercise that modify the risk of NAFLD differently. I heard about aerobic and resistance exercise. Yeah, there have been studies both on aerobic exercise and resistance exercise training, and we know that no matter whether you take aerobic exercise or resistance training, for instance 40 minutes three times a week for 12 weeks, then it can have an impact on the fat content in the liver. But there may be some advantages with regard to resistance exercise because you have an effect with less energy consumption, with less intensity. For some people with NAFLD who may have a poor fitness level or who may not tolerate aerobic exercise, it might be that resistance exercise could be beneficial for them. That could be maybe the choice for them. To the patients, what should we say? They will probably ask, how much exercise do I need to do in order to reduce either my risk of NAFL or my risk of progression? I would say that as much as you can do. But you get relatively more effect from going from zero exercise to a little exercise than you get from going from a lot of exercise to a little more. If you can aim for, let's say 30 minutes of exercise per day, and that could just be walking, that could be running, that could be that you use your bicycle as a mode of transportation forth and back to work or it could be even less. It could also be that you do some movements on your floor, some small strength training exercise programs. You have to do something, and if you just do it maybe a little everyday or maybe a little more three times a week, then there will be an effect within a few months. Sarcopenia, meaning the loss of muscles, has been implicated in high risk of progression and the end stage cirrhosis. How do we think that is? How does the muscle interact with our liver? It's very interesting that muscle loss will also lead to insulin resistance, which is a major risk factor for NAFLD. It may also be that loss of muscle mass will lead to less production of exercise factors, the so-called myokines, and that may mean that you have less ability to induce fat oxidation, so you will have more lipids in the blood that can be built into the liver. But when you then have developed your NAFLD, then you have an impaired liver function, which means that the factors produced by the liver, the so-called hepatokines, will also be affected. While this is still hypothetical, then we know that there are at least some hepatokines, for instance follistatin that is involved in regulating another factor, myostatin that is then again involved in building up the muscle, so you can speculate that if the liver suffers, it will produce little follistatin, then you will not be able to inhibit myostatin and the result will be the loss of muscle mass. Do you think then that that exercise in some years perhaps can be formulated into a pill? So rather than commuting to work, I can just take a pill? I think it was the actress Shea who said, if exercise was a pill everyone would like to take it. As a scientist, I believe she is right. But we know that when you exercise, there are several thousands of genes in the muscle that is activated, that is transcribed into mRNA. We also know that more than 1000 proteins are phosphorylated just in response to 10 minutes of bicycling. I think it's absolutely impossible that one compound, one pill, would be able to mimic all these effects of exercise. On the other hand, I think it's very likely that a pill, a compound, could mimic some of the effects of exercise, maybe could mimic some signal transduction, which could lead to that a pill could mimic the effect of exercise on metabolism, maybe on cognitive function, or maybe on muscle growth. I think that could very well be that the way we study the effects of exercise would also lead not just to advices to people, but also to identify new targets for medicine. During these recordings we are in a special time, we are in the COVID-19 crisis. This means that most people are not probably exercising as they should. How do you think we should enforce exercise during these times of COVID-19? I think it's pretty dangerous for people to be in isolation. It influences their mental health, but it also mimics their physical health. We know that just a few days of physical inactivity will lead to deterioration of our metabolism, and we will gain fat around the inner organs and visceral fat accumulation will increase. So I think it's very important to try to do some exercise at home. Maybe you can go into the internet and find some good home programs, both persistence training and some other kind of trainings you can do at home. But in our country, in Denmark, we have been allowed to be outdoor, and I think it's extremely important if you can every day go for a walk, maybe do some running, maybe take a bicycle, keep distance to people. I do it myself early in the morning. I do my run there where I don't meet people. So it can be absolutely safe for yourself and for others to do some exercise outdoor. That's my recommendation. Thank you very much for guiding us through how exercise might reduce our risk for NAFLD. As a summary, you think we can train our liver? I absolutely think we can train our liver. This is evidence-based advices that you have to exercise in order to protect your liver from NAFLD. If you already have fat in your liver, you can train this fat out of your body, out of your liver. What should you do? You should use your body when you go forth and back to work. Use your body as transportation, walk, maybe do some running, use your bicycle, do some resistance training. It's better to do a little than nothing, but you can absolutely train your liver. Thank you very much.
