All right, welcome everybody. It is 1030. Welcome to today's webinar. I am Dr. Lisa Chow from the University of Minnesota. And on behalf of the exercise physiology interest group, a leadership team, we're welcome to what we are excited to welcome everybody to our webinar, which is the power of movement, metabolic and vascular adaptations to exercise training. Next slide. So today, this is today's agenda, we will have introduction and announcements, we will have presentations from our star speakers, as well as a question and answer segment. Next slide. Notably, if you have questions, go ahead and submit it in the q&a box, which is not the same as the chat box. The chat box is for announcements and communication. The q&a box is for your specific questions. And what we will do at the end is to assemble all these questions that you have for a summary discussion of these talks. Next slide. This is our awesome leadership team. And I just want to thank all the members of the leadership team as well as a special shout out to Les Peckis to help organizing this webinar. Again, this is a great team, we have lots of opportunities for engaging in exercise physiology related work, you'll see that in a bit. There's a link in the chat. If you're interested about this particular exercise physiology group, as well as other interest groups at the ADA. Next slide. Just so you know, ADA professional members can join up the three interest groups of which we are one. And as a result, you actually have access to member exclusive webinars and webinar recordings, as well as recognition opportunities and volunteer leadership positions. Again, go to the link in the chat to learn more about ADA membership. Remember questions in the q&a, information in the chat. Next slide. Again, another benefit of ADA membership is connecting with members of the interest group. Again, see link in the chat below. So if you have an exercise physiology question, click on the forum, and then this will be sent out to your colleagues, and maybe they can come back with some great ideas for you. Next slide. These are some upcoming ADA professional webinars. The nutrition interest group is talking about culinary medicine as an ingredient for treating diabetes. And then the technology interest group is interested, we'll be talking about a year in review of diabetes related technology. Again, to look at the upcoming webinars, go ahead and go to the chat. Next slide. As it pertains to our group, we do have a hands on webinar. This is sponsored jointly by the ADA and the Helmsley Trust. And this is a really interesting webinar, looking at type one diabetes management in the setting of athletes, you know, high level sports. And the way this will be done is that we have two people invited. One is actually a college level athlete who has type one diabetes. And one is Ann Davis, endocrinologist from USC who has a lot of practice in, you know, clinical experience in managing people with type one diabetes. So if you've ever wondered how an athlete with type one diabetes is able to do what they do, this is a great opportunity to hear about that. Next slide. Now, if you happen to be within 10 years of completing your professional training, we would recommend and an ADA member, we would recommend that you consider applying for an early career abstract award. Specifically for us, this is with the exercise physiology interest group. So basically, if you're an ADA member, you're interested in exercise physiology, you're submitting an abstract to the ADA, you can get an award. And so submit your abstract by January 8, 2024. And we appreciate the chance to really highlight our early career members. Next slide. So today, I would like to welcome our presenters. First of all, we have Dr. Curtis Huey. He's an assistant professor at the University of Minnesota. Again, I'm also at the University of Minnesota. So we are colleagues. And he is a PhD scientist who was very interested in identifying metabolic nodes and pathways that can be targeted to prevent or treat metabolic diseases that burden our healthcare system. And specifically, he's very interested in talk that he'll be talking today about gluconeogenesis and liver lipid balance in the context of acute exercise, as well as the significance in how we might be able to use exercise to prevent fatty liver disease. After Dr. Huey presents, we'll have Dr. Liu, Mr. Liu present. He's a PhD student from the University of Alberta. And again, at the end of these presentations, we'll invite both of them on board for a Q&A section. So without further ado, we'd like to have Dr. Huey be our featured speaker. Go for it, Curtis, the stage is yours. Thank you, Lisa, for that introduction, and the leadership team for the opportunity to share some of our work with you-all. The work that I'm going to share with you today is largely from a publication in the American Journal of Physiology that we published earlier this year. That paper and the work that I'm going to share with you today really had two primary objectives. The first was to assess the role of gluconeogenesis in liver lipid homeostasis during an acute bout of exercise, and the second being to test whether gluconeogenesis is necessary for exercise training or regular exercise to prevent fatty liver. Now, we've become really interested in the liver metabolic responses to exercise because of the high prevalence of metabolic dysfunction associated with steatotic liver disease or MASLD. Currently, about 30 percent of the adult population has MASLD, and this is characterized by an accumulation of liver fat or liver steatosis. A subset of these individuals have what we call steatohepatitis or MASH. In addition to the built-up of fat, the livers are characterized by elevated inflammation, hepatocyte injury and dysfunction, and liver fibrosis. MASH is the concerning form of the disease. It is the progressive form of the disease. It increases one's risk for the development of advanced liver diseases such as cirrhosis and liver cancer. Making matters worse or compounding the high prevalence is, there's currently no approved pharmacotherapies for the disease. We really rely on lifestyle modification, which includes augmenting physical activity levels to prevent and treat MASLD. Now, a wealth of prior research, both in animal models and in humans show that aerobic exercise, as well as resistance training, is able to lower liver steatosis. When it comes to the other aspects of the disease, such as inflammation and fibrosis, there's some evidence that it is effective, but I think there still requires more study, maybe more randomized clinical trials to really reach consensus on this front. Now, at the bare minimum, exercise can prevent and treat liver steatosis, which is an important driver of disease from just fat buildup to liver cancer. Now, our lab really takes a look at the disease from a rather simplistic viewpoint, and that at a fundamental level, MASLD is an imbalance between lipid accretion in the liver, so the synthesis and storage, and lipid disposal, the catabolism and export. We've been really focused on the lipid disposal side of this equation. A major process in the liver that helps dispose of fat is called mitochondrial oxidative metabolism, which really refers to a cluster of pathways, which includes beta-oxidation, the TCA cycle, and oxidative phosphorylation. I often include gluconeogenesis in this cluster. Even though it isn't a bad breakdown pathway, it's really tightly associated with TCA cycle metabolism. If the TCA cycle increases, gluconeogenesis is often revved up as well. What we see with these pathways is that we have an early increase in the breakdown of fat in these pathways, but as the disease progress, there becomes an impairment. What happens is this helps facilitate the storage of excess fat in the liver. When it comes to exercise, a repeatedly observed finding is that regular physical activity is able to increase the capacity and flexibility of many of these oxidative metabolism pathways. This is partly due to increasing mitochondrial content. And while this is well-known, there's some gaps in knowledge that we still don't quite understand. And one, is this increased oxidative flux required for the benefits of exercise to prevent liver steatosis? And if it is important, what are the underlying mechanisms that allow these adaptations to occur? And so when trying to find inroads into the underlying mechanisms by which exercise is protective, we really looked at what we know a lot about, and that is what happens to liver metabolism during a single bout of exercise. And so as we all know here, during exercise, muscle glucose uptake is increased to support the energetic demands of muscle contraction. To maintain euglycemia, liver glucose output is stimulated. And this increased liver glucose production can come from three primary sources. It can come from glycogenolysis or stored glycogen. It can come from gluconeogenesis, sourced from glycerol, or it can come from gluconeogenesis that uses PEP, which is derived from PCA cycle metabolites. Now, the increase in gluconeogenesis is energetically costly. So there is a simultaneous increase in fat oxidation during exercise. And what this does, it helps support the energy demands of glucose production. And so if you take anything from this slide, it's that during exercise, an acute bout of exercise, gluconeogenesis is functionally coupled to fat oxidation. And so with this in mind, the objective of the work that I'm gonna share with you today was to really understand whether repeated bouts of increased gluconeogenesis to see if they are necessary for exercise training to lower liver fat. And so we often think of increased gluconeogenesis as being a negative. Well, we wanted to see whether there are instances where it could be a positive. And so to test this, we used a mouse model where we knocked out PEPCK in the livers of these mice. And this is an enzyme that really governs the ability of the liver to use TCA cycle intermediates to produce glucose. And so we use these knockout mice and wild-type littermates. We put them on a high-fat diet. And then we looked at these mice under resting conditions and during a single bout of treadmill running. We performed functional tests, we collected tissues, and we also performed stable isotope infusions to assess glucose and TCA cycle fluxes. So I just wanna quickly go over our infusion studies because I'm gonna present a few slides of this data. And so what we do is we catheterize the jugular vein and carotid artery of mice. The jugular vein catheter allows us to infuse isotope tracers, and the carotid artery allows us to acquire samples while the mice are both sedentary and while they are running. We infuse these isotopes for specific reasons. They are taken up by the liver, incorporated into both the TCA cycle and glucose-producing pathways. And if used for glucose production, we can see those labels in the circulating glucose that we sample. And ultimately, the labeling pattern of glucose tells us where it's coming from and the rates at which those pathways are producing glucose. Okay. So over the next couple of slides, I'm gonna show time courses where the zero time point is when mice are sedentary and the 10 through 30 minute time points are when mice are running on a treadmill. When it comes to blood glucose in these mice, we find that concentrations are similar between genotypes at rest, but during exercise, the knockout mice can't maintain euglycemia. And this is associated with a lower rate of glucose production during the exercise bout. Now, this lower glucose production isn't associated with changes in glycogen analysis or the contribution of glycogen to glucose production. As you can imagine, it is really linked to changes in gluconeogenesis. So what we see is that with wild type mice, exercise stimulates gluconeogenesis from glycerol, it stimulates gluconeogenesis from PEP, and it also stimulates the conversion of TCA cyclin intermediates into PEP. But the stimulation by exercise that we see in the wild type mice in these fluxes is not happening in the knockout animals. Consistent with this, the filling of the TCA cycle with nutrients is lower in the knockout animals at rest and during exercise. And TCA cycle flux, particularly as the exercise bout increases in duration, is also lower in the knockout animals. So what does this mean for fatty liver? Well, in the sedentary state, we see no differences in liver triacylglycerides between the genotypes. But immediately following exercise, lipid content is threefold higher in the knockout animals. And this persists into the refeeding phase after exercise. And so to summarize this, the last few slides, when we impair PEPCK function, we see lower glucose production. And this is largely due to the inability of exercise to stimulate gluconeogenesis and TCA cycle flux, which leads to the accumulation of liver fat. So during acute exercise, these results suggest that the stimulation of gluconeogenesis is necessary for lipid homeostasis. Now, the results of the acute exercise were really encouraging, but we really wanted to know whether gluconeogenesis was necessary for the adaptations to training. So was it necessary for training to prevent fatty liver? So we went back to our PEPCK knockout model. They were on a high-fat diet to promote fat buildup in the liver. And then we had these mice remain sedentary, or we trained them for six weeks. And so the exercise protocol was treadmill running 60 minutes a day, five days a week. After which we performed a series of phenotyping tests. Now, we didn't see any changes in PEPCK protein in the wild-type mice with training. When we looked at maximal running speed, it was similar between genotypes when they were untrained. There was a increase in maximal running speed in the wild-type mice with training, but this was prevented with the loss of PEPCK. So this is suggesting that PEPCK, or liver gluconeogenesis, is necessary for adaptations in exercise performance or aerobic capacity. And this is perhaps not unexpected. We need glucose to supply energy to working muscle. But this is really where the expected findings stop, and we start to get some findings that we weren't expecting. So when we looked at the liver fat, diacylglycerides were similar between genotypes when they were untrained. But training lowered diacylglycerides in the liver of knockout mice. When we looked at triacylglycerides, they were higher in the knockout mice when they were untrained. But training completely prevented this accumulation of fat. In fact, the loss of PEPCK might actually enhance the ability of exercise to lower fat in the liver. And so this was unexpected. It wasn't in line with what was happening during acute exercise. And so ongoing research in the lab is interested in why this is occurring. And over the next couple of slides, I'm just gonna highlight some areas of research in the lab. Earlier in the talk, when I was referring to oxidative metabolism, I left out one important pathway, and that is ketogenesis, or the disposal of fat to ketone bodies. Now, we didn't see any differences between genotypes in ketogenic enzymes, but as we all know, enzyme expression or protein levels don't often associate with flux. And so to get an idea of changes in ketogenic flux, we really looked at circulating beta-hydroxybutyrate over multiple physiological conditions. We looked at it during fasting, sedentary state. We looked at it during exercise, post-exercise fasting, but it really wasn't until the refeeding phase after exercise that we saw this slowed decline in beta-hydroxybutyrate in the knockout animals, suggesting that the disposal of fat persisted after exercise through ketogenesis in the knockout animals. Now, anytime we study exercise, we can't look at organs in a silo. We did see some markers of metabolic adaptations in skeletal muscle. Liver glycogen was increased in the knockout trained animal. Training also increased citric synthase activity in the knockout animals, which is a marker of mitochondrial content. And consistent with the citric synthase activity, we see increased OXFOS protein levels in the knockout trained animals, particularly at complex three and four. Now, in addition, we also see that exercise can limit the gain in body weight and fat mass in mice, but this is particularly striking in the knockout animals. And so to summarize this last set of data, in mice lacking PEPCK, exercise is still effective at reducing liver fat. In fact, it might be enhanced. Now, this could be due to persistent disposal of fat through ketogenesis, or it might be due to extra hepatic adaptations that limit supply of fat to the liver. And so these results suggest that liver gluconeogenesis is not necessary for training to lower fat. They also highlight a really area of interest in our lab right now is that liver metabolism can perhaps augment adaptations to exercise in extra hepatic tissue. So we're currently interested in liver source nutrients and how they affect muscle adaptations to training. And if I can speculate on this last point, you know, there's a real boom in trying to enhance the efficacy of exercise training, the timing of exercise. So morning versus afternoon, before or after eating, the timing of co-therapy, so insulin and metformin. And perhaps we should consider liver metabolism and how these affect liver metabolism, particularly in individuals with MASLD when prescribing exercise protocols. With that, I'd like to thank our collaborators, our funding sources, and in particular, Farrell Rome, who was really the main driver of the data that I shared with you today. Thank you, Curtis. That was a really, really good talk. It's intriguing. That wasn't quite what you expected, the difference between acute and chronic exercise, but we'll talk more in the Q&A, but I just wanna say that's a great presentation. All right, we'll have our next speaker and then we'll do the Q&A at the end. We have Hao-Hsuan Liu, who's a PhD student at the University of Alberta. His research interests include the impact of mental stress, sedentary behavior, and exercise on arterial health. And today he'll be presenting a publication that he had, which is a detailed analysis of existing systemic reviews focusing on the strengths, gaps, and limitations. And with this, he will provide a comprehensive overview of the impact of exercise training on arterial stiffness in adults. So this is a review of systematic reviews. All right, it's all yours. Go for it. Thank you. Can you see my slides properly? Good. Okay, morning, everyone. So today I'll be talking about a review study collected in our lab entitled The Impact of Exercise Training on Pulse Wave Velocity in Healthy and Clinical Populations, a Systemic Review of Systemic Reviews. So what is pulse wave velocity? It is simply defined as the speed of the forward traveling pressure wave between two sides within the arterial system. And the speed of this wave is thought to reflect arterial stiffness. And this picture here shows how we measure pulse wave velocity. So first, arterial pulse wave is measured at two arterial sites. In this example, in the carotid artery and the femoral artery. And the pulse transit time is also measured by determining the time between the foot of the carotid wave and the foot of the femoral wave. And then the pulse wave velocity is calculated as the distance between these sites divided by the pulse transit time. So a higher pulse wave velocity is indicative of a stiffer artery. And a lower pulse wave velocity indicates that arteries have maintained their elasticity and compliance, allowing them to absorb and buffer the pressure generated by the heartbeat. And the arterial stiffness is determined by the structural and functional characteristics of an artery. And structurally, stiffening of the artery wall is determined by the arterial extracellular metrics, including the collagen elastin ratio. And moreover, it has been shown that vascular endothelial function is also associated with arterial stiffness. And even acute changes in endothelial function can have an impact on arterial stiffness. So the pulse wave velocity is most commonly measured between the carotid and femoral arteries because it can reflect aortic stiffness. And aorta is the most elastic artery and plays a huge hemodynamic role, not only as a tunnel, but also as a buffer for position in the blood pressure and flow. And a healthy aorta will exhibit a low pulse wave velocity. And in previous meta-analyses, it has been demonstrated that an increase of one meter per second increase in carotid femoral pulse wave velocity is associated with a 15% higher risk of cardiovascular disease and all-cause mortality. And these highlights the significant impact of arterial stiffness on overall health outcomes. Moreover, pulse wave velocity can also be measured between the brachial and the tibial arteries, known as the brachial-ankle pulse wave velocity. And it reflects the systemic or the whole-body arterial stiffness. And in East Asian countries, brachial-ankle pulse velocity has gained widespread use and accumulating evidence from these regions has shown the prognostic significance of the brachial-ankle pulse velocity with each one meter per second increase associated with a 12% increase in the risk of cardiovascular disease mortality and a 6% increase in the risk of all-cause mortality. And in addition to the carotid femoral and brachial-ankle segments, pulse wave velocity can also be measured in other peripheral arterial sites, such as the femoral to ankle segment. And it's worth noting that measuring peripheral arterial stiffness is a common practice and may provide insights into the compliance of the different arterial segments but the prognostic value of the peripheral pulse velocity is still limited and conflicting. So we are all aware of the numerous benefits of exercise for cardiovascular health and exercise is not only considered a first-line intervention for managing various cardiovascular disease risk factors, but also plays a crucial role in improving overall cardiovascular well-being. And given this, the impact of exercise training on arterial stiffness measured by pulse velocity has attracted a lot of interest and has been extensively explored in intervention studies. And over the past two decades, numerous systematic reviews have been conducted to summarize the effects of exercise training on arterial stiffness. However, these reviews have reported inconsistent evidence regarding the impact of exercise training on pulse velocity. And one possible explanation for these divergent findings could be the variations in the population study and the heterogeneous characteristics of the exercise training interventions employed in different studies. So to gain a more comprehensive understanding of the effects of exercise training on pulse velocity and to address inconsistencies in the previous reviews, it is essential to conduct an umbrella review. And the umbrella review, essentially a review of reviews, involves the systematic compilation of the data from multiple existing reviews. And it also offers the advantage of not only providing a comprehensive overview, but also allowing us to, allowing the systematic comparison and contrast of the findings across diverse populations and various exercise interventions. Therefore, last year, our lab conducted an umbrella review to thoroughly examine and summarize the findings from available systematic reviews regarding the impact of exercise training on pulse velocity in adults. And we also investigated whether the impact of exercise training on pulse velocity differs across various training characteristics and the different populations of interest. So in August, 2022, we conducted a comprehensive database search for relevant systematic reviews in five databases. And our search was focused exclusively on studies involving adults without any restrictions on the health status of the participants. We excluded the reviews that studied the acute effects or single sessions of exercise from our analysis. And to be included in our analysis, selected reviews had to have pulse velocity as a primary outcome measure. And we didn't put any restrictions on the assessment size for pulse velocity. And finally, we exclusively included published systematic reviews and didn't incorporate any literature into our analysis. So after the database search, we identified a total of 44 eligible systematic reviews, including over 17,000 participants. And these 44 reviews collectively included findings from 187 unique primary studies involving 6,700 unique participants. And within these 44 systematic reviews, we categorized them into different populations of interest. So first, we found 19 studies in general adults, which included healthy adults or a heterogeneous group consisting of both healthy adults or individuals with one or more health conditions. And the nine studies focused on patients with kidney disease. So chronic kidney disease or the end-stage renal disease. And seven studies focused on individuals with known cardiovascular disease or at a higher risk of developing cardiovascular disease. And three studies were specific to type 2 diabetes. There were also six studies focused on individuals with different conditions, including post-menopausal females, adults with obesity, patients with autoimmune rheumatic diseases, and patients with spinal cord injuries. And overall, the average study quality scored approximately a nine out of 11, with the majority of the studies demonstrating a moderate to high level of quality. So now we'll move on to the results, starting with the effects of exercise training in the general population, general adults. So out of the 18 reviews focusing on general adults, six studies investigated the impact of aerobic training on pulse velocity, and all of them reported a reduction in pulse velocity. And meta-analysis conducted in these studies indicated a reduction ranging from 0.52 to 0.75 meter per second, which could potentially translate to an estimated of six to 10% decrease in cardiovascular disease mortality risk. And then examine the effects of resistance exercise. These studies revealed that low to moderate intensity resistance training can effectively enhance pulse velocity. In contrast, high intensity resistance training had no impact on pulse velocity. And despite the positive effects of both aerobic and low to moderate intensity resistance training on pulse velocity, the combination of aerobic and resistance training didn't result in any positive velocity reduction. And we speculated that this discrepancy might be attributed to the variations in the intensity of resistance exercises within different combined training programs. And finally, a few reviews have demonstrated that the beneficial effects of stretching and yoga on pulse velocity. Unfortunately, no meta-analysis has been conducted to quantitatively assess the effects of stretching or yoga. And nine reviews investigate the impact of exercise training on pulse velocity in patients with kidney disease. And most of these reviews had a limited sample sizes and included a very small number of individual studies. However, a very recent meta-analysis, which synthesized the findings from 18 randomized control trials involving over 800 unique participants revealed a decrease of 0.56 meter per second in carotid femoral pulse velocity following exercise training. And this reduction might correspond to an estimated 7% reduction in cardiovascular disease mortality. Notably, this meta-analysis didn't assess the comparative effects of different types or intensities of exercise on pulse velocity, leaving the optimal type of exercise training for improving arteriosclerosis in this population still unclear. Additionally, several reviews specifically explored the effects of intradialytic exercise on pulse velocity and intradialytic exercise involves physical activity performed by patients with end-stage renal disease during their hemodialysis sessions. And one systematic review indicated that intradialytic exercise resulted in significant reduction of 1.13 meters per second in pulse velocity, potentially translating to a substantial 15 percent risk reduction in cardiovascular disease mortality. So in summary, exercise in general has the potential to reduce arterial stiffness in patients with kidney disease and should be considered as a part of their care. However, the most effective exercise training programs for this population is still an ongoing area of investigation. Okay, now let's turn our focus to patients with cardiovascular disease or those at a high risk of cardiovascular disease. So once again, most studies reported favorable outcomes associated with aerobic exercise training, and magnitude of reduction ranged from 0.4 to 0.7 meters per second, which corresponds to an estimated 6 to 10 percent reduction in cardiovascular disease mortality risk. Conversely, the majority of the studies indicated that resistance training had no significant impact on pulse velocity. However, the combination of aerobic and resistance training resulted in a substantial reduction in pulse velocity ranging from 0.74 to 1.15 meters per second, and this reduction is linked to approximately a 10 to 15 percent decrease in cardiovascular disease mortality risk. And in light of these findings, while aerobic exercise contributes to be the predominant modality in cardiac rehabilitation, the inclusion of the resistance training should be considered alongside aerobic exercises, and this combination could offer more comprehensive health benefits. And the three studies specifically reviewed the impact of exercise training on pulse velocity in patients with type 2 diabetes. And interestingly, neither aerobic training nor combined training showed significant improvements in our articulativeness in this population. However, it's important to note that this lack of effectiveness might be attributed to the low level of evidence or low quality of the current individual studies. So there is a clear need for high quality randomized control trials to further study the effects of exercise training on pulse velocity in patients with type 2 diabetes. And while there is currently no evidence showing the direct beneficial effects of exercise on arterial stiffness in this population, another UNBRAD review conducted by our lab has demonstrated that low to moderate intensity aerobic training or resistance training can improve vascular endothelial function in patients with type 2 diabetes. And considering the overall health benefits of exercise training, such as glycemic and blood pressure control, it is still important to recommend exercise training for patients with type 2 diabetes. However, more research is necessary to better understand the specific impact of exercise on pulse velocity in this population. And two reviews, including one meta-analysis, have examined the impact of combined aerobic and resistance training on brachial-ankle pulse velocity in the post-menopausal females. And both reviews concluded that this type of exercise training leads to a reduction in pulse velocity. And it is important to note that brachial-ankle pulse velocity is a strong predictor of major adverse cardiovascular events in post-menopausal females. Therefore, the findings from the meta-analysis are particularly important. And the meta-analysis demonstrated that brachial-ankle pulse velocity decreased by 1.18 meters per second following exercise training. And this reduction in pulse velocity corresponds to approximately a 12% risk reduction in cardiovascular disease mortality. And based on these findings, it is highly recommended that post-menopausal females incorporate both aerobic and resistance exercise into their lifestyle practices. And this combination of exercise modalities can have a positive impact on arterial health and potentially reduce the risk of cardiovascular events. So in this umbrella review, our original goal was to identify the optimal exercise training program for each population and their study. However, we discovered that this goal is unrealistic due to the significant heterogeneity in exercise intervention characteristics across the existing literature. Moreover, there is inconsistency in the reporting of exercise training characteristics in individual level studies, as noted in previous reviews. And to address this issue, future individual studies, as well as reviews, should consistently report detailed and specific exercise intervention characteristics while adopting a standardized approach to examine the effects of exercise training. And a subgroup analysis should be conducted to isolate different components of the intervention. And this will provide more meaningful exercise recommendations that can be applied in real-world practice. Additionally, it's worth mentioning that most systematic reviews included in our umbrella review combined positive velocity results from different arterial segments and even the combined positive velocity data with other measures of arterial stiffness. Unfortunately, this, of course, significantly limits our ability to interpret the clinical value of many reviews. And considering that only carotid, femoral, and brachial-ankle positive velocity have demonstrated prognostic value in predicting cardiovascular events or post-mortality, it is crucial for future reviews to perform standardized subgroup analysis specifically on these clinically significant measures of arterial stiffness or positive velocity. Finally, we have some take-home messages. So, in general, various forms of exercise have been shown to improve positive velocity in the general population. Aerobic training, low-to-moderate intensity resistance training, as well as stretching or yoga can all contribute to reducing arterial stiffness. And for individuals with cardiovascular disease or those at high increased risk of cardiovascular disease, aerobic training or a combination of aerobic and resistance training has been found to be particularly effective in improving positive velocity. And when this comes to patients with chronic kidney disease or end-stage renal disease, exercise training has shown positive effects on positive velocity, although more research is needed to determine the specific impact of different types or intensities of training in these cases. Furthermore, post-male and post-female females can benefit from combined aerobic and resistance training, which has been shown to improve positive velocity in this population. And in conclusion, our UNBRAD review underscores the positive impact of exercise training on positive velocity and arterial stiffness and implementing aerobic training, resistance training, or a combination of both can have significant benefits for individuals across various populations. And thank you for this. All right. Well, thank you so much. We'll have Curtis show up too. And now we'll start our Q&A section. Thank you so much, Haoxuan, for your talk. Well, let's start with the questions. So the question we first have is for Dr. Hsiu-Yi Curtis. Did you do any assessments of mitochondrial respirations in the liver tissue samples itself? So meaning when you took out the liver tissue, did you directly measure mitochondrial respiration? That's a great question. We haven't done that yet. We, the one challenge is we were trying to get, using tissue to do a bunch of assays, but certainly doing respiratory, which we could really target the electron transport chain system would be key. And we're really interested in not just the liver, but also the muscle in the inoculum mice, where we saw a lot of changes in OxBas-related protein. All right. I have a question for Haoxuan. This is my question. Did you see any correlation between the change in pulse wave velocity and maybe a change in VO2 max? I don't know if you had that data, but namely, if you had a very good exercise response in terms of training regards to VO2 max, you also see a sort of a correlation in the improvement in pulse wave velocity. I have to say, I can't hear you. So we, in this review, we didn't extract any VO2 data, but I think in the literature, there has been a lot of studies showing that the positive, or the negative correlation between VO2 peak and pulse velocity, and also endothelial function. So there are definitely benefits of improving fitness and reducing arterial stiffness. And I think this is a question primarily for Curtis. What is the effect of high-calorie drinks taken during exercise on liver fat content? Any long-term effects? Great question. So the, you know, the exercise supplement field is sort of outside my wheelhouse, but I can give you some speculation on my part. And so high-calorie drinks or high fructose and glucose drinks, we know promote, at least long-term, can promote liver fat deposition. You know, the one unique thing about when combined with exercise is that some of these drinks can also enhance insulin levels. And so there is some data out there to suggest that enhancing eating before food or these high fructose glucose energy drinks can enhance insulin. And this sort of drives glucose and lipid disposal, not just in the liver, but in the muscles. So it's sort of a complicated story that it might not be all bad when combined with exercise. So kind of, here's just a question from my standpoint. You know how when people have a meat, they're going to carb load and they carb load their spaghetti the night before and such. Do you think it works? I think, I think there's a, you know, long line of research suggesting that you can enhance glycogen stores in the muscle and this can enhance endurance or performance. I mean, there are contradictory papers as always, but I think it's, there's a lot of research that's showed the benefits of it. Yeah. Okay. All right. We've got a question for Haoxuan. Were there any studies that use peripheral pulse wave velocity assessment, like the femoral to ankle? And do you think the response to training in peripheral pulse wave velocity would be different than central pulse wave velocity? Yeah, that's a really good question. So in many reviews, including our Amber, they combined the central and peripheral pulse velocity data. And some studies did subgroup analysis and they showed that peripheral pulse velocity may be respond better than central to exercise training because peripheral arteries inherently, they are stiffer than the central arteries. So the start at a higher level of stiffness. So they may respond better to exercise training compared to the central arteries that, because they are already like very elastic. So there may be a foreign fact of the baseline stiffness of the arteries. Thank you. The question I also have for you, is that your effect size that you see is quite modest. How does you reconcile that with like the variability of just measuring the pulse wave velocity? Just when you measure the same person five times, you're going to get some variability just from that measurement. So how significant is the effect that size that you observe versus just the day-to-day variability in the pulse wave velocity measurement? So the effect size we extracted from this are like most of the weighted mean difference were mean difference. So they are not Cohen's d or any like other effects metrics. So I think we can comment on like the clinical significance of this virus. We know one meter per second increase in carotid femoral pulse velocity is associated with 15% increase in all-cause mortality. So we can only like speculate the clinical significance of our findings. But in terms of like day-to-day variability, for me, I've never done any pulse wave velocity data studies like in our lab. We have only done review studies. So I need to like study more about the day-to-day variability. Thank you. Anybody questions? And if you can't somehow put it in the Q&A, put it in the chat, send it to me, and I'll be happy to answer that. So I have a question for Curtis then while we sort of wait. Do you think that, did you do anything special with the diet in the context of your exercise studies? Did you just feed them a regular child diet? Or did you consider like if you fed them a high fat diet, you might be able to exacerbate observed differences? So that particular study was a high fat diet because we really did want to increase liver fat to try to get that effect. But we've done it on a similar exercise protocols on a low fat chow diet. And we see similar effects as well. So sometimes the, you know, with mice, sometimes the low fat diets are actually a little bit easier because they're much better runners than after they've been on a high fat diet for long periods of time. And did you quantify their fitness by VO2 max before and after training? That's a great question. So we used our maximal running speed as a marker of that. And so in mice, maximal running speed is positively correlated with VO2 max. So that is sort of what we've used as our marker. But certainly having the VO2 max, which we can do, would be a more direct measurement for sure. Right. Any questions from anybody else in the group? If not, we'd like to thank our amazing speakers. Thanks to the ADA staff for organizing this. And thanks to Liz, especially for taking the lead and making this going really smoothly. So thank you everybody for coming. And again, there's a lot more ADA seminars. Please check in the chat, as well as our athletes and type 1 diabetes seminar in January. So thank you again, everybody for coming. Thank you. Bye. Thank you.

Exercise training

Gluconeogenesis

Liver lipid balance

Fatty liver disease

Arterial stiffness

Pulse wave velocity

Aerobic training

Resistance training

Health conditions