This is part five of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the symposium "Metabolic Flexibility in Health and Disease" by Ayland Letsinger. 

Carbohydrate and fat are the dominant fuel sources for energy production in our bodies. Everyone needs energy – from the most sedentary individual to the most elite athletes. On the one hand we often have trouble getting athletes to eat enough food given their high daily energy needs, while on the other hand many sedentary people who do not move much are consuming more energy than they need. In a world where individuals crave the best diet for their needs, Lawrence Spriet, Ph.D., FACSM, of the University of Guelph led a symposium on metabolic flexibility at ACSM’s Conference on Integrated Physiology of Exercise. The discussion provided science-based advice for elite athletes, sedentary people and individuals with obesity and type II diabetes. 

Dr. Spriet opened with a complex image outlining the major pathways that allow the tissues in the human body (i.e. skeletal muscle) to use fat and carbohydrate to produce energy. He commented that, “My students hate when I show this diagram, but it is important to see the whole picture of fat and carbohydrate metabolism in order to make informed choices. They call it the ‘Dreaded Metabolic Pathway Diagram.’” The key point was clear: the impressive and tremendous “flexibility” to alternate between carbohydrate or fat utilization to meet the energy demands of the body is critical for optimal performance and health. And this is most impressive when responding to single and repeated bouts of exercise. The following impressive cast of scientists supported this point with elegantly performed studies.   

Carbs: Friends or Foe? 

The high fat/low carbohydrate diet is being touted as a game changer for improving endurance performance and has become common among non-athletes. Louise Burke, Ph.D., FACSM, presented very convincing evidence showing that low carb/high fat diets had no clear benefit for low intensity exercise and simultaneously ruined high intensity performance in endurance athletes. She let the audience know her studies were followed by a barrage of angry Twitter warriors calling her work poor and claiming the studies were not long enough for the athletes to adapt to the diet. However, Dr. Burke and others have shown humans on a low carb/high fat diet DO in fact adapt and have increased ability to utilize energy from fat. Although, primarily using fat as fuel is less metabolically efficient than using glucose (the total energy yield is lower), glycogen (stored glucose) utilization is impaired, and certain high intensity points in endurance races (think of uphill portions or the final sprint to the finish line) requires carbohydrate usage for optimal performance.  In other words, the improved utilization of fat for fuel means losing vital efficiency in glucose utilization. 

The work of Bret Goodpaster, Ph.D., in studying individuals with type 2 diabetes, has revealed a decreased ability to store fuel (fat and carbohydrate) after a meal and severely impaired metabolic flexibility in utilization of fat and glycogen.  Simple exercise and weight loss programs, individually and together, restored much of the lost ability to store fuel and the flexibility to use it in skeletal muscle and the whole body. The messages were clear: you have to move more, and don’t overeat.  

Deb Muoio, Ph.D., closed the symposium by giving a great illustration of how important the mitochondria are for maintaining metabolic flexibility and health. These are the organelles in all of our cells where the majority of our energy is produced. The mitochondrial volume in cells increases when you are physically active and shrink when you are not. She showed that metabolic inflexibiliy is like a traffic jam in the common carbohydrate and fat utilization pathways that exist in the mitochondria. In simpler terms, a high fat/low carb diet is not the secret to health improvement, as exercise is proven to improve optimal metabolic function.

Finding the “perfect diet” for everyone is likely fleeting, but all four presenters agreed on a similar theme: the body’s ability to utilize both carbohydrates AND fats is critical for optimal performance and health. If you decide to remove either substrate, your body will miss that critical fuel.


Read part 1 of this series: "Can Exercise Fill the Reductionist Gap? Reflections on Dr. Michael Joyner's Keynote."
Read part 2 of this series: "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate." 
Read part 3 of this series: "Exercise and Energy Restriction to Improve Health: Recent Research." 
Read part 4 of this series: "Molecular Transducers of Physical Activity (MoTrPac) Update." 


Ayland Letsinger is a Doctoral Student at Texas A&M University. Ayland was presented with an award for poster presentation at ACSM's Conference on Integrative Physiology of Exercise in 2018 for the abstract titled: A High Fat/High Sugar Diet Alters the Gastrointestinal Metabolome in a Sex Dependent Manner. 

This is part four of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the update regarding the Molecular Transducers of Physical Activity investigation by John Quindry, Ph.D., FACSM. 

In case you missed the Molecular Transducers of Physical Activity (MoTrPac) update at ACSM’s Conference on Integrative Physiology of Exercise (IPE) meeting in San Diego, here’s what you need to know:

Presenters were Marcas Bamman, Ph.D., FACSM, and Karyn Esser, Ph.D., FACSM, two principle investigators in the massive $170 million multi-site investigation. Funded by the NIH Common Fund, both human and animal research will be conducted over the next several years.

The primary points of the IPE update were to convey the phase one timeline and final methodologies determined by the MoTrPac steering committee (the investigators and outside consultants). Dr. Bamman provided updates on the human models (2,600 research volunteers), while Dr. Esser detailed the animal arms (many hundreds of Fisher 344 rats, 19 organs sampled post mortem). I encourage you to check out the particulars for yourself.

Another key point of the update was to share that, in the coming years, outside investigators can petition for tissue access in a grant-specific way. There is no doubt that the outcome of this work will set the stage for the next generation of mechanistic understanding of exercise and physical activity on total body health. In question, however, is whether the respective human and animal study designs will be robust enough to flush out all the potential new leads. The answer is probably not. By virtue of scale, Drs. Bamman and Esser conveyed that this research phase is the best overall study design, but a compromise to say the least. During the Q&A, many top scientists within our ranks raised key points of concern, all of which were conceded by the presenters.

We’re taught in first semester graduate school that no study design is an “end all,” and MoTrPac is no exception. People may find this alarming given the $170 million price tag, but it is worth noting that this investment in preventative exercise has been long coming and is a fraction of a percent of past expenditures directed to curative medicine. I happened to be on the NIH ad hoc review of the original MoTrPac submissions, and we debated many of these same points in the room and wondered more among ourselves quietly in smaller groups during the down time. Having managed my own grant budgets for years, I’m still amazed that $170 million is just as finite a sum as the grant totals for other studies. I trust that the outcomes are going to be revealing and that the next generation scientists in the field will leverage these findings into **BILLION** dollar follow-up studies and even more impactful future discoveries.  

Read part 1 of this series: "Can Exercise Fill the Reductionist Gap? Reflections on Dr. Michael Joyner's Keynote."
Read part 2 of this series: "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate." 
Read part 3 of this series: "Exercise and Energy Restriction to Improve Health: Recent Research." 

John Quindry, Ph.D., FACSM, is a member of the faculty at the University of Montana, Department of Health and Human Performance. He served as a co-planner of ACSM's Conference on Integrative Physiology of Exercise. 

This is part three of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the symposium "Exercise and Energy Restriction to Improve Health: The Crossroads of Energetics and Protein Turnover" by Karyn Hamilton, RD, PhD, FACSM.

What an honor to be part of the IPE symposium “Exercise and Energy Restriction to Improve Health: The Crossroads of Energetics and Protein Turnover” on Friday afternoon. Despite the happy hour time slot and the outstanding weather in San Diego providing a tempting distraction, the session was well-attended.

Dr. Colin Selman served as a perfect chairperson for the event, keeping the speakers on schedule and on task. One notable characteristic of this session, and all of the symposia I attended, was how perfectly focused the collective presentations were—as if the speakers had been working together on the content for weeks.

Dr. John Speakman runs two research groups: one in Beijing China and the other in Aberdeen, Scotland. His contribution to the symposium focused on altering energetics with exercise and energy restriction to impact healthspan. One overriding question of Dr. Speakman’s talk, and this area of research in general, is: Can interventions such as energy restriction and exercise increase human lifespan? Dr. Speakman made compelling arguments about genetic pleiotropy and provided terrific “food for thought” that even attendees who do not focus their work on this area of research could appreciate, such as “What makes you healthy and live a long time, might also make you run more!” I heard some attendees quipping that it doesn’t really matter if calorie restriction makes humans live longer when it makes the adorable grey mouse lemur live longer.

Dr. Tracy Anthony of Rutgers University did an outstanding job of framing the cutting-edge research she does with the integrated stress response, in the context of “Exercise is Medicine.” She pointedly provided an overview of how Exercise is Medicine is actually hormesis in action; The complex physiological stresses evoked by exercise stimulate integrated adaptations that, in turn, provide protection or “resilience” to future stresses. As Dr. Anthony pointed out, “The metabolic path to health is complicated,” but the work in her lab is going a long way to help unravel the complex responses to exercise and other energetic stresses.

I was the final speaker in the symposium—quite intimidating to follow Drs. Speakman and Anthony. This was a perfect opportunity to provide an overview of our findings using four long-lived murine models that have in common both extended healthspan and activation of energetic stress signaling. The work our research team carried out clearly demonstrates activation of mechanisms favoring mitochondrial proteostasis during energetic stress, with the trade-off being slower cell proliferation or growth.

ACSM’s Conference on Integrative Physiology of Exercise provided the perfect opportunity to share published and unpublished data demonstrating the importance of understanding interactions between exercise and pharmacological interventions that also extend healthspan. It is fair to say that if you are interested in the crossroads between energetics and health, you should keep your eye on work emerging from the labs directed by the speakers in this symposium.

Website for Dr. Speakman's lab at the University of Aberdeen. 
Information on Dr. Anthony's lab. 
Website for Dr. Hamilton's lab. 

Read part 1 of this series: "Can Exercise Fill the Reductionist Gap? Reflections on Dr. Michael Joyner's Keynote."
Read part 2 of this series: "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate." 


Karyn L. Hamilton, RD, PhD, FACSM, is a member of the faculty at Colorado State University. She serves as a professor in the Health and Exercise Science department, the Director of the Translational Research on Aging and Chronic Disease Lab and Associate Director of the Center for Healthy Aging. She earned her bachelor's and and master's degrees at Montana State University and her Ph.D. at the University of FLorida where she worked in Scott Powers' lab. 

This is part two of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the debate, "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training?" between Ron Evans, Ph.D., and John Hawley, Ph.D.

The first debate of ACSM’s Conference on Integrative Physiology of Exercise, “Are exercise 'mimetics' a realistic substitute for exercise training?” is in the books, and it was a conversation starter to say the least. Pro-mimetic commentary was provided by Ronald Evans, PhD, of the Salk Institute, while John Hawley, PhD, of the Mary MacKillop Institute for Health Research gave counter arguments on behalf of exercise.

My humble opinion of the session is that both presenters approached the topic from opposite ends on a spectrum of the human condition, albeit providing variable interpretations of the same data. Imagine a Venn diagram where Evans’ mimetics and Hawley’s exercise intersect modestly, but with spirited debate over common ground. At the crux of this particular debate is PPARg, or peroxisome proliferator-active receptor gamma – a name only a scientist could love.

If you haven’t been keeping score at home, PPAR activation is central to many of the well described adaptive responses to aerobic exercise. Staying out of the molecular weeds, it is fair to summarize that PPAR activation results in dramatic alteration in metabolic function to the extent that human exercise capacity is improved in elite athletes, mall walkers and type 2 diabetics alike. Perhaps ten seconds after characterizing this cellular pathway, the search for a medicinal approach to PPAR activation (agonist) began. Think of the potential: countless lives saved or improved, Nobel prizes, swimming pools of cash! Proof of concept experiments were first conducted by Ron Evans’ research team in which “couch potato” mice receiving newly formulated PPAR activators were suddenly running literal circles around their untreated cage mates.

Remarkable as this landmark discovery was, it immediately raised the ire of some in the exercise field. Correction – media-generated overstatements that “exercise in a pill had been discovered” rightfully inflamed the those of us who promote physical activity and exercise a as means to improved health.

So what’s the wrinkle? In short, PPAR agonists (and presumably other exercise mimetics not discussed currently), amazing as they are, are not as robust a stimulus when compared to formal exercise. The metabolic and exercise performance responses to the current forms of these pills are many fold lower than good old fashioned exercise training (think ACSM prescriptive criteria for furry critters).

But you want to know who won the debate.

Sorry, but they both did. Evans very clearly defended the position that PPAR activation, should it be scalable to humans, would be revolutionary to those who can’t exercise due to disease, severe deconditioning or extreme risk for precipitating a medical event with exercise. More pragmatically, most people in the developed world won’t exercise, and there is a solid rationale to suspect that this pill is better than nothing.

On the other side of the argument, Hawley deftly defended the fact that there is no substitute for exercise. No single pill discovered to date can provide the robust multi-tissue, multi-system benefits of a brisk walk.

And by the nature of this meeting, Hawley came to the podium wearing the white hat, but that doesn’t mean Evans had a black hat. Indeed, journalistic irresponsibility in overstating the claims of exercise mimetics has nothing to do with Evans’ position. Evans’ intentions are as altruistic as Hawley’s and it’s worth noting that Evans promoted exercise alongside his mimetic discoveries. In the end Evans mostly spoke to diseased applications while Hawley addressed healthier populations. The Venn diagram overlap, still to be negotiated, pertains to those that won’t exercise—a debate for another day.

Read Part 1: "Can exercise fill the reductionist gap? Reflections on Dr. Michael Joyner's Keynote."

John Quindry, Ph.D., FACSM, is a member of the faculty at the University of Montana, Department of Health and Human Performance. He served as a co-planner of ACSM's Conference on Integrative Physiology of Exercise. 

This is part one of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the Opening Keynote delivered by Michael Joyner, M.D, FACSM. 

Having just sat through the Michael Joyner keynote talk, the opening event at the ACSM Integrative Physiology of Exercise meeting in San Diego, I’m left wondering if I can go back to graduate school. (I just checked with my wife…the answer is “NO!”) But Joyner’s talk was that inspiring.

As with any engaging academic lecture, Dr. Joyner had three points to make—the first being that the luminaries of modern science have crafted more than a few hollow promises about how omics and big data will solve societies medical woes. Indeed, there is a drug discovery gap, a health outcomes gap and the undeniable reality that when science removes a singular mechanism from a biological system, parallel mechanisms take up the slack.

Dr. Joyner’s second point was refreshingly made from the perspective that genetics do not rule all outcomes. In essence, humans are “plastic.” In true Joyner fashion, the “exercise is good medicine” message was packaged in a nuanced way that I’ll admit I’ve never before heard. The middle point was topped by reassuring the audience that phenotyping is hard—a strong call to do more research that overlaps mechanistic, parallel human and animal models, clinical and translational.

The final point was perhaps best of all: Dr. Joyner shared eight novel research ideas. Each idea, if performed correctly, would likely prove to be a landmark study. Are you sure I can’t go back to grad school?! He also coined the “Joyner criteria” for whether regenerative medicine is a success: benefits of new interventions should exceed that of exercise training.

So yes, I was inspired. Safe to state that in a room of smart people (everyone has or is earning a terminal degree of one type or another), Dr. Joyner is quite probably the brightest. His ability to bring food for thought is unparalleled within the ACSM umbrella. His talk was definitely worth the price of admission.     

See this news release for more details on Dr. Joyner's keynote. 

John Quindry, Ph.D., FACSM, is a member of the faculty at the University of Montana, Department of Health and Human Performance. He served as a co-planner of ACSM's Conference on Integrative Physiology of Exercise.